Fused heterotricyclic compounds, process for preparing the compounds and drugs containing the same

ABSTRACT

The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula, a pharmacologically acceptable salt thereof or hydrates thereof.  
                 
 
     Wherein A, B and D are the same as or different from each other and each represents a group represented by the formula —(CR 1 R 2 ) m — (wherein R 1  and R 2  are the same as or different from each other and each represents a C 1-6  alkyl group etc.), —NR 3 — (wherein R 3  represetns hydrogen etc.) etc.; E and G are the same as or different from each other and each represents a group represented by the formula —(CR 6 R 7 ) p — (wherein R 6 and R 7  are the same as or different from each other and each represents hydrogen etc.; and p represents an integer of 0, 1 or 2); J represents a carbon atom or nitrogen atom, each substituted with C 1-6  alkyl group optionally substituted with a halogen atom, etc.; K and L are the same as or different from each other and each represents carbon atom or nitrogen atom; M means hydrogen, a halogen atom, an optionally substituted C 1-6  alkyl group etc.; and the partial structure  means a single or double bond.

FIELD OF THE INVENTION

[0001] The present invention relates to a tricyclic fused heterocycliccompound having corticotropin-releasing-factor receptor antagonisticactivity, a pharmacologically acceptable salt thereof and hydratesthereof, and a process for preparing its and pharmaceutical use thereof.

PRIOR ART

[0002] Corticotropin-releasing-factor (hereinafter, referred to as‘CRF’) is a neuropeptide comprising 41 amino acids, and isolated fromsheep hypothalamus (Science, 213, 1394 (1981)) and, then, its presencewas confirmed in a rat (Proc. Natl. Acad. Sci. USA, 80, 4851 (1983)) anda human being (EMBO J. 5, 775 (1983)). CRF is the most abundant inpituitary gland and hypothalamus and is widely distributed in a brainsuch as cerebral cortex, cerebellum and the like. In addition, in aperipheral tissue, CRF is confirmed to be present in placenta, adrenalgland, lung, lever, pancreas and digestive tract (J. Clin. Endocrinol.Metab., 65, 176 (1987), J. Clin. Endocrinol. Metab., 67, 768 (1988),Regul. Pept., 18, 173 (1987), peptides, 5 (Suppl. 1), 71 (1984)). Twosubtypes CRF1 and CRF2 are present in a CRF receptor, and a CRF1receptor is reported to be distributed at a large amount in cerebralcortex, cerebellum, olfactory bulb, pituitary gland, almond nucleus andthe like. Recently, two subtypes CRF2α and CRF2β were confirmed to bepresent in a CRF2 receptor, and it was found that a CRF2α receptor isdistributed in hypothalamus, septal area and choroid plexus at a largeamount and a CRF2β is distributed in a peripheral tissue such asskeletal muscle and in a cerebrovascular part in central tissue (J.Neuroscience, 15 (10) 6340 (1995); Endocrinology, 137, 72 (1996); BBA,1352, 129 (1997)). Since each receptor is distributed differently, it issuggested that its role is also different. CRF is produced in andsecrete from hypothalamus and promotes the release ofadrenocorticotropic hormone (ACTH) by stress (Recent Prog. Horm. Res.,39, 245(1983)). CRF serves as a neurotransmitter or a neuromodulatoralso in a brain and integrates electrophysiology to stress, autonomicnerve and action, in addition to a role to incretion (Brain Res. Rev.,15, 71, (1990); Pharmacol. Rev., 43, 425 (1991)).

[0003] Currently, CRF is thought to be involved in a variety of diseasesand there are reports as follows;

[0004] 1) CRF in a cerebrospinal liquid in a depression patient is at ahigher value as compared with a healthy man (Am. J. Psychiatry, 144(7),873 (1987)).

[0005] 2) A CRF-mRNA level in hypothalamus in a depression patient is ahigher value as compared with a healthy man (Am. J. Psychiatry, 152,1372 (1995)).

[0006] 3) A CRF receptor is decreased in a cerebral cortex of a personwho commits suicide (Arch. Gen. Psychiatry, 45, 577 (1988)).

[0007] 4) A rise of ACTH in a plasma is small in a depression patientupon administration of CRF (N. Engl. J. Med., 314, 1329 (1986)).

[0008] 5) CRF in a cerebrospinal liquid of a certain anxiety patientsuch as compulsion disorder, posttraumatic stress disorder, teulettsyndrome etc. is a higher value as compared with a healthy man (Arch.Gen. Psychiatry, 51, 794 (1994); Am. J. Psychiatry, 154, 624 (1997);Biol. Psychiatry, 39, 776 (1996)).

[0009] 6) A rise of ACTH in a plasma is small in a panic disorderpatient upon administration of a CRF (Am. J. Psychiatry, 143, 896(1986)).

[0010] 7) An anxiety behavior is recognized when CRF is administered ina brain of an experimental animal (Brain Res., 574, 70 (1992); J.Neurosci., 10 (1), 176 (1992)). In addition, many anxiety behavior arerecognized in a CRF overexpressing mouse as compared with a normalanimal (J. Neurosci., 14 (5), 2579 (1994)).

[0011] 8) CRF blue spotted nucleus is decreased by administration of ananti-anxiety agent (J. Pharmaco. Exp. Ther., 258, 349 (1991)). Inaddition, α-helical CRF (9-41) of a peptidic CRF antagonist exerts ananti-anxiety behavior in an animal model (Brain Res., 509, 80 (1990);Regulatory Peptize, 18, 37 (1987); J. Neurosci., 14 (5), 2579 (1994)).

[0012] 9) α-Helical CRF (9-41) of a peptidic CRF antagonist inhibits anabnormal behavior due to abstinence of dependency drug such as alcoholand cocaine (Psychopharmacology, 103, 227 (1991)).

[0013] 10) CRF suppresses a sexual behavior of a rat (Nature, 305, 232(1983)).

[0014] 11) CRF is thought to be involved in sleep disorder because itreduces rat's sleep (Pharmacol. Biochem. Behav., 26, 699 (1987)).

[0015] 12) α-Helical CRF (9-41) of a peptidic CRF antagonist inhibitsdisorder of a brain and brain wave abnormality due to brain ischemia andactivation of NMDA receptor (Brain Res., 545, 339 (1991), Brain Res.656, 405 (1994)).

[0016] 13) CRF awakens a brain wave and induces convulsion (Brain Res.,278, 332 (1983)).

[0017] 14) CRF in a cerebrospinal liquid of a schizophrenia patient is ahigher value as compared with a healthy man (Am. J. Psychiatry, 144(7),873 (1987)).

[0018] 15) CRF in a cerebral cortex in an Alzheimer disease, Parkinsondisease or progressive supranuclear palsy is reduced (Neurology, 37, 905(1987)).

[0019] 16) CRF in a Huntington disease ganglion is reduced (Brain Res.,437, 355 (1987), Neurology, 37, 905 (1987)). In addition, it has beenfound that administration of CRF in a rat enhances learning and memory(Nature, 378, 384 (1995); Neuroendocrinology, 57, 1071 (1993)).

[0020] 17) CRF in a cerebrospinal liquid in an amyotrophic lateralsclerosis patient. In a CRF overexpressing mouse, oversecretion of ACTHand adrenal gland steroid hormone occurs and abnormality similar toCushing syndrome such as muscular atrophy, alopecia and infertility(Endocrinology, 130(6), 3378 (1992)).

[0021] 18) CRF in a cerebrospinal liquid in an anorexia nervosa patientis a higher value as compared with a healthy man, and a rise of ACTH ina plasma is small in an anorexia nervosa upon administration of CRF (J.Clin. Endocrinol. Metab., 62, 319 (1986)).

[0022] 19) CRF suppresses eating in an experimental animal(Neuropharmacology, 22 (3A), 337 (1983)). In addition, α-helical CRF(9-41) of a peptidic CRF antagonist improved decrease in eating in ananimal model due to stress load (Brain Res. Bull., 17 (3), 285 (1986)).

[0023] 20) CRF suppressed weight gain in a hereditary obesity animal(Physiol. Behav., 45, 565 (1989)).

[0024] 21) It is suggested that the lowness of a CRF value and obesitysyndrome are related (Endocrinology, 130, 1931 (1992)).

[0025] 22) It is suggested that eating inhibition and weight loss actionof a serotonine reuptake inhibiting agent is via release of CRF(Pharmacol. Rev., 43, 425 (1991)).

[0026] 23) CRF acts on centralness and peripherallness, weakensconstriction of a stomach and reduces stomach excretion ability(Regulatory Peptides, 21, 173 (1983); Am. J. Physiol., 253, G241(1987)). In addition, α-helical CRF (9-41) of a peptidic CRF antagonisthas the recovery action on the functional decrease of stomach due toabdominal operation (Am. J. Physiol., 262, G616 (1992)).

[0027] 24) CRF promotes secretion of bicarbonate ions in stomach,decreases gastric acid secretion, and at the same time, inhibits coldconstraint stress ulcer (Am. J. Physiol., 258, G152 (1990)). Inaddition, ulcer is increased in a non-constraint animal by CRFadministration (Life Sci., 45, 907 (1989)).

[0028] 25) CRF suppresses small intestine transport, promotes largeintestine transport and induces defecation. In addition, α-helical CRF(9-41) of a peptidic CRF antagonist has the inhibitory action ondecrease in gastric acid secretion, decrease in stomach excretion,decrease in small intestine transport and asthenia in large intestine(Gastroenterology, 95, 1510 (1988)).

[0029] 26) In a healthy man, mental stress increases a gas and bellyachedue to anxiety and gastrectasis and CRF reduces a threshold of uncomfort(Gastroenterol., 109, 1772 (1995); Neurogastroenterol. Mot., 8, 9(1996)).

[0030] 27) In an irritable bowel syndrome patient, large intestinemovement is excessively exasperated by administration of CRF as comparedwith a healthy man (Gut., 42, 845 (1998)).

[0031] 28) Administration of CRF increases blood pressure, heart rateand body temperature. In addition, α-helical CRF (9-41) of a peptidicCRF antagonist inhibits elevation of blood pressure, heart rate and bodytemperature (J. Physiol., 460, 221 (1993)).

[0032] 29) In an inflammatory part of an experimental animal and a jointliquid of a rheumatoid arthritis patient, production of CRF is locallyincreased (Science, 254, 421(1991); J. Clin. Invest., 90, 2555 (1992);J. Immunol., 151, 1587 (1993)).

[0033] 30) CRF induces degranulation of a mast cell and exasperatesvessel permeability (Endocrinology, 139(1), 403 (1998); J. Parmacol.Exp. Ther., 288 3), 1349 (1999)).

[0034] 31) Also in an autoimmune thyroiditis patient, CRF is detected(Am. J. Pathol., 145, 1159 (1994)).

[0035] 32) When CRF is administered to an experimental autoimmunecerebrospinal meningitis rat, progression of symptom of palsy and thelike was remarkably inhibited (J. Immunol., 158, 5751 (1997)).

[0036] 33) In a system for culturing pituitary gland adenocarcinoma ofan acromegaly patient, urocortin (analogue of CRF) increased secretionof a growth hormone (Endocri, J., 44, 627 (1997)). In addition, CRFstimulates secretion of cytokin such as interleukin 1 and interleukin 2(J. Neuroimmunol., 23, 256(1989); Neurosci. Lett., 120, 151(1990)).

[0037] 34) Activity of natural killer cell and increase of T lymphocyteare decreased by administration of CRF and load of stress. α-HelicalCRF(9-41) of a peptidic CRF antagonist improves decrease in the functionof immune cells due to administration of CRF and stress load(Endocrinology, 128(3), 1329 (1991)).

[0038] 35) Breathing is remarkably increased by administration of CRF(Eur. J. Pharmacol., 182, 405 (1990)). In an advanced aged patientequipped with a long term artificial inhaler, animus of breathing andinsomnia were recognized by administration of CRF (Acta Endcrinol.Copenh., 127, 200 (1992)).

[0039] From the above study reports, a CRF antagonist can be expected toexert the excellent effects in treating or preventing depression anddepressive symptom including great depression, monostotic depression,recurrent depression, infant tyrannism by depression and postpartumdepression, mania, anxiety, generalized anxiety disorder, panicdisorder, phobia, compulsive disorder, posttraumatic stress disorder,Tourette syndrome, autism, emotional disorder, sentimental disorder,bipolar disorder, cyclothymia, schizophrenia, Alzheimer disease,Alzheimer type senile dementia, neurodegenerative disease such asParkinson disease and Huntington disease, multi-infarct dementia, seniledementia, neurotic anorexia, appetite asthenia and other diet disorder,obesity, diabetes, alcohol dependence, pharmacophilia to cocaine,heroin, benzodiazepine etc., drug or alcohol withdrawal, sleep disorder,insomnia, migraine, stress headache, myotonic headache, ischemicneuropathy, excitation toxic neuropathy, cerebral apoplexy, progressivesupranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis,muscular convulsion, chronic fatigue syndrome, mental social growthfailure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodictorticollis, muscular convulsion, neck-shoulder-arm syndrome, primaryglaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosisincluding cardioneurosis, intestinal neurosis and bladder neurosis,peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'sdisease, diarrhea, coprostasis, postoperational ileus, gastrointestinalfunction abnormality associated with stress and neural vomiting,hypertension, cardiovascular disorder including neural angina,tachycardia, congestive cardioplegia, hyperpnea syndrome, bronchialasthma, apnea syndrome, infant sudden death syndrome, inflammatorydisorder (for example, rheumatoid arthritis, bone arthritis, lumbagoetc.),pain, allergic disease (for example, atopic dermatis, eczema,urticaria, psoriasis etc.), impotence, climacteric disorder,fertilization disorder, infertility, cancer, immune function abnormalityupon infection with HIV, immune function abnormality by stress,hemorrhagic stress, Cushing syndrome, thyroid function disorder,encephalomyelitis, acromegaly, incontinence, osteoporosis etc. There isa report on a CRF antagonist, for example, a peptide-type CRF receptorantagonist in which a part of an amino acid sequence of a human being orother mammal is altered or deleted, and it is reported that theantagonist shows the ACTH release inhibitory action and anti-anxietyaction of the antagonist (Science, 224, 889 (1984), J. Pharmacol. Exp.Ther., 269, 564 (1994), Brain Research Reviews, 15, 71 (1990)). However,it must be said that, from a viewpoint of pharmacokinetics such as thechemical stability in vivo, the bioavailability and the transferabilityto brain, the utility value thereof as a medicament is low.

[0040] On the other hand, regarding a non-peptide type CRF antagonist,there is the following report:

[0041] 1) A compound represented by the formula:

[0042]  (wherein R¹ represents NR⁴R⁵ etc.; R² represents a C₁₋₆ alkylgroup etc.; R³ represents a C₁₋₆ alkyl group etc.; R⁴ represents a C₁₋₆alkyl group etc.; R⁵ represents a C₁₋₆ alkyl group etc.; and Arrepresents phenyl etc.), a stereoisomer thereof, or pharmaceuticallyacceptable acid addition salts thereof (WO97/29109).

[0043] 2) A compound represented by the formula:

[0044]  (wherein a broken line represents a single or double bond; Arepresents CR⁷ etc.; B represents NR¹R² etc.; J and K are the same as ordifferent from each other and each represents nitrogen atom etc.; D andE are the same as or different from each other and each representsnitrogen atom etc.; G denotes nitrogen atom etc.; R¹ represetns a C₁₋₆alkyl group etc.; R² represents a C₁-C₁₂ alkyl group etc.; and R⁷represents hydrogen atom etc.) or a pharmacologically acceptable saltthereof (WO98/08847).

[0045] 3) An anilinopyrimidine compound described in WO95/10506, apyrazolopyrimidine compound described in WO95/34563, a pyrazole compounddescribed in WO94/13661, a pyrazole and pyrazolopyrimidine compounddescribed in WO94/13643, aminopyrazole described in WO94/18644, apyrazolopyrimidine compound described in WO94/13677, a pyrrolopyrimidinecompound described in WO94/13676, a thiazole compound described inEP-659747, EP-611766, an anilinopyrimidine compound described in J. Med.Chem., 39, 4358 (1996), an anilinotriazine compound described in ibid.39, 3454 (1996), a thienopyrimidine compound described in WO97/29110etc.

[0046] As described above, there is desired the provision of a CRFreceptor antagonist which is useful as a medicament. However, amedicament which shows the excellent CRF receptor antagonism, andsatisfies the pharmacological activity, the dose, the safety etc. as amedicament and effectively acts clinically has not been found. That is,an object of the present invention is to search and find such theexcellent CRF receptor antagonist.

DISCLOSURE OF THE INVENTION

[0047] According to the above-mentioned, circumstances, the presentinventors studied intensively. As a result, they successfullysynthesized a novel tricyclic fused heterocyclic compound represented bythe following formula, a pharmacologically acceptable salt thereof orhydrates thereof and, further surprisingly, found that the compound hasan excellent CRF antagonist action and the object can be attained. Thus,they have accomplished the present invention.

[0048] Wherein A, B and D are the same as or different from each otherand each represents:

[0049] (1) heteroatom selected from nitrogen atom, oxygen atom andsulfur atom;

[0050] (2) formula —(CR¹R²)_(m)— (wherein R¹ and R² are:

[0051] (i) the same as or different from each other and each representshydrogen atom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynylgroup, a C₁₋₆ alkoxy group, a C₃₋₈ cycloalkyl group, a C₁₋₆ alkoxy C₁₋₆alkyl group, a C₃₋₈ cycloalkyl C₁₋₆ alkyl group or a C₁₋₆ alkyl-arylgroup, or R¹ and R² may be bound together to form a 3- to 8-memberedring;

[0052] (ii) R¹s are bound together so that adjacent —CR¹R²-s form acarbon-carbon double bond, that is, a partial structure represented byformula —CR²═CR²—; or

[0053] (iii) R¹ and nitrogen atom may form a bond so that an adjacentnitrogen atom and —CR¹R²— form a partial structure represented by theformula —N═CR²— (R² is as defined above); and

[0054] m is 0 or an integer of 1 to 4);

[0055] (3) —CO—;

[0056] (4) —CS—;

[0057] (5) —NR³— (wherein R³ represents:

[0058] (i) hydrogen atom;

[0059] (ii) formula —COR⁴ (wherein R⁴ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group);

[0060] (iii) —S(O)_(n)R⁵ (wherein R⁵ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group; and n is an integer of 0, 1 or2);

[0061] (iv) a C₁₋₁₀ alkyl group optionally substituted with any of oneor more groups defined in the following A group;

[0062] (v) a C₂₋₁₀ alkenyl group optionally substituted with any of oneor more groups defined in the following A group;

[0063] (vi) a C₂₋₁₀ alkynyl group optionally substituted with any of oneor more groups defined in the following A group;

[0064] (vii) an optionally substituted aryl group; or

[0065] (viii) a C₃₋₈ cycloalkyl group optionally fused with optionallysubstituted benzene ring and optionally substituted with a C₁₋₄ alkylgroup);

[0066] (6) —SO—; or

[0067] (7) —SO₂—,

[0068] E and G are the same as or different from each other and eachrepresents:

[0069] (1) a heteroatom selected from nitrogen atom, oxygen atom andsulfur atom;

[0070] (2) formula —(CR⁶R⁷)_(p)— (wherein R⁶ and R⁷ are:

[0071] (i) the same as or different from each other and each representshydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group optionallysubstituted with a C₁₋₄ alkyl group, an optionally substituted arylgroup or an optionally substituted heteroaryl group;

[0072] (ii) R⁶s are bound together so that adjacent —CR⁶R⁷-s form acarbon-carbon double bond, that is, a partial structure represented byformula —CR⁷═CR⁷— (R⁷ is as defined above); or

[0073] (iii) R⁶ and nitrogen atom may form a bond so that an adjacentnitrogen atom and a group —CR⁶R⁷— form a partial structure representedby —N═CR⁷— (R⁷ is as defined above); and

[0074] p is an integer of 0, 1 or 2,

[0075] provided that when both E and G are groups —(CR⁶R⁷)_(p)— at thesame time, p dose not represent 0 and at least one of E and G representgroup —CR⁶R⁷—);

[0076] (3) —CO—;

[0077] (4) —CS—;

[0078] (5) —NR⁸— (wherein R⁸ represents:

[0079] (i) hydrogen atom;

[0080] (ii) formula —COR⁹ (wherein R⁹ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group);

[0081] (iii) —S(O)_(n)R¹⁰ (wherein R¹⁰ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group; and n is an integer of 0, 1 or2);

[0082] (iv) a C₁₋₁₀ alkyl group optionally substituted with any of oneor more groups defined in the following A group;

[0083] (v) a C₂₋₁₀ alkenyl group optionally substituted with any of oneor more groups defined in the following A group;

[0084] (vi) a C₂₋₁₀ alkynyl group optionally substituted with any of oneor more groups defined in the following A group; or

[0085] (vii) a C₃₋₈ cycloalkyl group optionally fused with an optionallysubstituted benzene ring and optionally substituted with a C₁₋₄ alkylgroup);

[0086] (6) —SO—; or

[0087] (7) —SO₂—;

[0088] J represents:

[0089] (1) nitrogen atom or

[0090] (2) carbon atom or nitrogen atom which is substituted with anyone or more selected from:

[0091] (i) hydrogen atom;

[0092] (ii) amino group;

[0093] (iii) cyano group;

[0094] (iv) a C₁₋₆ alkyl group optionally substituted with a halogenatom;

[0095] (v) a C₁₋₆ alkylaminosulfonyl group;

[0096] (vi) an optionally substituted aryl group; and

[0097] (vii) an optionally substituted saturated or unsaturatedheterocyclic ring,

[0098] K and L are the same as or different from each other and eachrepresents carbon atom or nitrogen atom,

[0099] a ring formed by K, E, G, J and L in the above formula (I)represents a saturated or unsaturated 5- or 6-membered ring,

[0100] M represents:

[0101] (1) hydrogen atom;

[0102] (2) halogen atom;

[0103] (3) cyano group;

[0104] (4) a C₁₋₆ alkyl group optionally substituted with any of one ormore groups defined in the following A group;

[0105] (5) formula —NR¹¹R¹²— (wherein R¹¹ and R¹² are the same as ordifferent from each other and each represents:

[0106] (i) hydrogen atom;

[0107] (ii) any group defined in the following A group;

[0108] (iii) a C₁₋₆ alkyl group optionally substituted with any of oneor more groups defined in the following A group;

[0109] (iv) a C₁₋₄ alkylacyl group;

[0110] (v) an optionally substituted aryl C₁₋₄ alkyl group;

[0111] (vi) an optionally substituted heteroaryl C₁₋₄ alkyl group;

[0112] (vii) an optionally substituted aryl group; or

[0113] (viii) an optionally substituted heteroaryl group);

[0114] (6) —OR¹³ (wherein R¹³ represents hydrogen atom, a C₁₋₆ alkylgroup optionally substituted with any of one or more groups defined inthe following A group, a C₁₋₄ alkylacyl group, an optionally substitutedaryl C₁₋₄ alkyl group, an optionally substituted heteroaryl C₁₋₄ alkylgroup, an optionally substituted aryl group or an optionally substitutedheteroaryl group);

[0115] (7) —S(O)_(q)R¹⁴ (wherein R¹⁴ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group; and q is an integer of 0, 1 or2);

[0116] (8) an optionally substituted C₂₋₁₀ alkenyl group;

[0117] (9) an optionally substituted C₂₋₁₀ alkynyl group;

[0118] (10) a C₁₋₆ alkoxy group optionally substituted with any of oneor more groups defined in the following A group;

[0119] (11) a C₁₋₆ alkylthio group optionally substituted with any ofone or more groups defined in the following A group;

[0120] (12) an optionally substituted aryl group; or

[0121] (13) an optionally substituted heteroaryl group,

[0122] the partial structure

represents a single or double bond, and

[0123] the A group defined above represents the group consisting of:

[0124] (1) halogen atom,

[0125] (2) hydroxy group,

[0126] (3) nitro group,

[0127] (4) cyano group,

[0128] (5) carboxy group,

[0129] (6) a C₁₋₆ alkyloxycarbonyl group,

[0130] (7) a group represented by the formula —S(O)_(r)R¹⁵ (wherein r isan integer of 0, 1 or 2; and R¹⁵ represents:

[0131] (i) hydrogen atom;

[0132] (ii) a C₁₋₆ alkyl group;

[0133] (iii) a group represented by the formula —NR¹⁶R¹⁷ (wherein R¹⁶and R¹⁷ are the same as or different from each other and each representshydrogen atom, a C₁₋₆ alkyl group optionally substituted with anoptionally substituted aryl group, a C₁₋₄ alkylacyl group, an optionallysubstituted aryl C₁₋₄ alkyl group, an optionally substituted heteroarylC₁₋₄ alkyl group, an optionally substituted aryl group or an optionallysubstituted heteroaryl group);

[0134] (iv) an optionally substituted aryl C₁₋₄ alkyl group;

[0135] (v) an optionally substituted aryl group;

[0136] (vi) an optionally substituted heteroaryl C₁₋₄ alkyl group; or

[0137] (vii) an optionally substituted heteroaryl group);

[0138] (8) a group represented by the formula —NR¹⁸R¹⁹ (wherein R¹⁸ andR¹⁹ are the same as or different from each other and each representshydrogen atom, a C₁₋₆ alkyl group or a C₁₋₄ alkylacyl group);

[0139] (9) a C₁₋₆ alkyl group;

[0140] (10) a C₁₋₆ alkoxy group;

[0141] (11) a C₃₋₈ cycloalkyl group optionally substituted with a C₁₋₄alkyl group;

[0142] (12) a C₁₋₄ alkoxy C₁₋₆ alkyl group;

[0143] (13) a saturated 3- to 8-membered heterocyclic ring optionallysubstituted with a C₁₋₄ alkyl group;

[0144] (14) an optionally substituted aryl group; and

[0145] (15) an optionally substituted heteroaryl group, provided that inthe above definition,

[0146] (1) the case where both K and L are nitrogen atoms; and

[0147] (2) the case where K is nitrogen atom, L is carbon atom, A and Bare groups represented by the formula —(CR¹R²)_(m)— (wherein both R¹ andR² represent hydrogen atoms; and m is 1), and J is carbon atomsubstituted with any group selected from:

[0148] (i) amino group;

[0149] (ii) cyano group;

[0150] (iii) aminosulfonyl group in which the nitrogen atom issubstituted with a straight or branched C₁₋₆ alkyl group; and

[0151] (iv) 1H-tetrazol-5-yl group, are excluded.

[0152] That is, the first essential feature of the present invention is:

[0153] (1) a compound represented by the above formula(I), apharmacologically acceptable salt thereof or hydrates thereof, andfurther,

[0154] (2) in the above (1), B and/or D may be nitrogen atom, oxygenatom, sulfur atom, or a group represented by the formula —NR³—, —CO— or—(CR¹R²)_(m)— (wherein R¹, R², R³ and m have the same meanings asdefined above);

[0155] (3) in the above (1), A and/or B may be a group represented bythe formula —(CR¹R²)_(m)— (wherein R¹, R² and m have the same meaningsas defined above);

[0156] (4) in the above (1), D maybe nitrogen atom, oxygen atom, sulfuratom or a group represented by the formula —NR³— (wherein R³ has thesame meaning as defined above);

[0157] (5) in the above (1), D may be a group represented by the formula—NR³— (wherein R³ is as defined above);

[0158] (6) in the above (1), the partial structure -A

B

D- may be a group represented by the formula:

—CH₂—CHR²—CHR²—; —CH₂—CHR²—NR³—; —CH═CR²—CHR²—

—CH₂—CHR²—O—; —CH₂—CHR²—S—; —CR²═N—NR³—

—CH═CR²—NR³—; —CR²═CR²—NR³—; —NH—CR²═CR²—

—N═CR²—CHR²—; —(CH₂)₂—CR²—NR³—; —(CH₂)₃—CR²—NR³—

—CH₂—CO—NR³—; —CO—NR³—CO—; —CO—NR³—NR³—

—NR³—CO—NR³—; —CH₂—CS—NR³—; —CS—NR³—CS—

—CS—NR³—NR³— or —NR³—CS—NR³—

[0159]  wherein R² and R³ are as defined above, and R² and R³ are thesame as or different from each other;

[0160] (7) in the above (6), R² and/or R³ are the same as or differentfrom each other and each may be hydrogen atom, a C₁₋₆ alkyl group, aC₂₋₆ alkynyl group, a C₁₋₆ alkoxy C₁₋₆ alkyl group or a C₁₋₆ alkyl-arylgroup;

[0161] (8) in the above (1), K may be nitrogen, and L may be carbon;

[0162] (9) in the above (1), K and L may be carbon;

[0163] (10) in the above (1), E or G may be nitrogen;

[0164] (11) in the above (1), E or G may be a group represented by theformula —(CR⁶R⁷)_(p)— (wherein R⁶ and R⁷ have the same meanings asdefined above);

[0165] (12) in the above (1), the partial structure

E

G

may be a group represented by the formula —[CH(R⁷)]₂—, —N═CR⁷—, —CR⁷═N—,—[CH(R⁷)]₃—, —CR⁷═CR⁷—CR⁷═, —N═R⁷—CR⁷═ or —CR⁷—CR⁷—N═ (wherein R⁷ hasthe same meaning as defined above);

[0166] (13) in the above (12), R⁷ may be the same as or different fromeach other and each may be hydrogen atom or a C₁₋₆ alkyl group;

[0167] (14) in the above (1), J may be a carbon atom or nitrogen atomsubstituted with any one group selected from (1) aryl group and (2)saturated or unsaturated heterocyclic ring,

[0168] (15) in the above (1), J may be a carbon atom or nitrogen atomsubstituted with any one group selected from phenyl group, pyridylgroup, thienyl group and furyl group;

[0169] (16) in the above (1), J may be a carbon atom or nitrogensubstituted with a phenyl group optionally substituted with one to threegroups selected from a halogen atom, a C₁₋₆ alkyl group optionallysubstituted with a halogen atom and a C₁₋₆ alkoxy group;

[0170] (17) in the above (1), M may be (1) hydrogen atom, (2) a halogenatom, (3) cyano group, (4) a C₁₋₆ alkyl group optionally substitutedwith any one or more groups listed in the above A group, (5) a C₁₋₆alkoxy group optionally substituted with any one or more groups listedin the above A group or (6) an amino group optionally substituted withany one or more groups listed in the above A group;

[0171] (18) in the above (1), M may be hydrogen, a C₁₋₆ alkyl group, aC₁₋₆ alkoxy group or a C₁₋₆ alkylthio group;

[0172] (19) in the above (1), M may be methyl group;

[0173] (20) in the above (1), A and B may be a group represented by theformula —(CR¹′R²′)_(m′)— (wherein R¹′ and R²′ are the same as ordifferent from each other and each represents hydrogen atom or a C₁₋₆alkyl group; and m′ represents an integer from 1 to 3), D may be a grouprepresented by the formula —NR³— (wherein R³ has the same meaning asdefined above), E may be nitrogen atom, and G may be a group representedby the formula ═CR⁸— (wherein R⁸ has the same meaning as defined above),

[0174] (21) in the above (1), the partial structure -A

B

may be a group represented by the formula —CR²═CR²— (wherein R²represents hydrogen atom or a C₁₋₆ alkyl group), D may be a grouprepresented by the formula —NR³— (wherein R³ has the same meaning asdefined above), E may be nitrogen atom, and G may be a group representedby the formula ═CR⁸— (wherein R⁸ has the same meaning as defined above);and

[0175] (22) in the above (1), A may be a group represented by theformula —(CR¹R²)_(m′)— (wherein R¹ and R² are the same as or differentfrom each other and each represents a C₁₋₆ alkyl group; and m′represents an integer from 1 to 3), B may be a group represented by theformula —CO— or —CS—, D may be a group represented by the formula —NR³—(wherein R³ has the same meaning as defined above), E may be nitrogenatom and G may be a group represented by the formula ═CR⁸— (wherein R⁸has the same meaning as defined above),

[0176] a compound relating to the present invention may be:

[0177] (23) a compound represented by the formula:

[0178]  (wherein R², R³ and the partial structure

has the same meanings as defined above; M′ represents hydrogen atom, ahalogen atom or a C₁₋₆ alkyl group; R⁷′ represents hydrogen atom or aC₁₋₆ alkyl group; W represents hydrogen atom, amino group, cyano group,a C₁₋₆ alkyl group, a C₁₋₆ alkylaminosulfonyl group, an optionallysubstituted aryl group, or an optionally substituted saturated orunsaturated heterocyclic ring), a pharmacologically acceptable saltthereof, or hydrates thereof;

[0179] (24) a compound represented by the formula:

[0180]  (wherein R², R³, R⁷′, M′, W′ and the partial structure

are as defined above), a pharmacologically acceptable salt thereof orhydrates thereof;

[0181] (25) a compound represented by the formula:

[0182]  (wherein R², R³, R⁷′, M′, W′ and the partial structure

are as defined above), a pharmacologically acceptable salt thereof orhydrates thereof;

[0183] (26) a compound represented by the formula:

[0184]  (wherein R², R³, R⁷′, M′, W′ and the partial structure

are as defined above), a pharmacologically acceptable salt thereof orhydrates thereof;

[0185] (27) a compound represented by the formula:

[0186]  (wherein R², R³, R⁷′, M′, W′ and the partial structure

are as defined above), a pharmacologically acceptable salt thereof orhydrates thereof; and

[0187] (28) a compound represented by the formula:

[0188]  (wherein R², R³, R⁷′, M′, W′ and the partial structure

are as defined above), a pharmacologically acceptable salt thereof orhydrates thereof, and

[0189] (29) in the above (1), the compound may be any one selected from:

[0190]8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0191]8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0192]3-mesityl-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0193]8-benzyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,3-e]pyrimidine;

[0194]3-mesityl-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0195]3-mesityl-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0196]2-ethyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0197]8-(1-ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethyl-3-pyridyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0198] 6-mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine;

[0199]9-(cyclopropylmethyl)-8-ethyl3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine;

[0200] 2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-yl)butyl methylether;

[0201]1-(1-ethylpropyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridine;and

[0202]2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,5-naphthyridin-1-yl]butylmethyl ether.

[0203] In addition, the second essential feature of the presentinvention is:

[0204] (30) a medicament which comprises the compound as described inthe above (1), a pharmacologically acceptable salt thereof or hydratesthereof, and further,

[0205] (31) the medicament described in the above (30) may be an agentfor treating or preventing diseases to which corticotrophin-releasingfactor (hereinafter, referred to as “CRF”) and/or a CRF receptor relate;

[0206] (32) the medicament described in the above (30) may be a CRFreceptor antagonist;

[0207] (33) the medicament described in the above (30) may be an agentfor treating or preventing depression, depressive symptom or mania;

[0208] (34) in the above (33), the depressive symptom may be greatdepression, monostotic depression, recurrent depression, infanttyrannism by depression or postpartum depression;

[0209] (35) the medicament described in the above (30) may be an agentfor treating or preventing anxiety, generalized anxiety disorder, panicdisorder, phobia, compulsive disorder, posttraumatic stress disorder,Tourette syndrome, autism, emotional disorder, sentimental disorder,bipolar disorder, cyclothymia or schizophrenia;

[0210] (36) the medicament described in the above (30) may be an agentfor treating or preventing peptic ulcer, irritable bowel syndrome,ulcerative colitis, Crohn's disease, diarrhea, coprostasis,postoperational ileus, gastrointestinal function abnormality associatedwith stress or neural vomiting; and

[0211] (37) the medicament described in the above (30) may be an agentfor treating or preventing Alzheimer disease, Alzheimer type seniledementia, neurodegenerative disease, multi-infarct dementia, seniledementia, neurotic anorexia, diet disorder, obesity, diabetes, alcoholdependence, pharmacophilia, withdrawal, sleep disorder, insomnia,migraine, stress headache, myotonic headache, ischemic neuropathy,excitation toxic neuropathy, cerebral apoplexy, progressive supranuclearpalsy, amyotrophic lateral sclerosis, multiple sclerosis, muscularconvulsion, chronic fatigue syndrome, mental social growth failure,epilepsy, head trauma, spinal trauma, graphospasm, spasmodictorticollis, muscular convulsion, neck-shoulder-arm syndrome, primaryglaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis,hypertension, cardiovascular disorder, tachycardia, congestivecardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome,infant sudden death syndrome, inflammatory disorder (for example,rheumatoid arthritis, bone arthritis and lumbago), pain, allergicdisease (for example, atopic dermatis, eczema, urticaria and psoriasis),impotence, climacteric disorder, fertilization disorder, infertility,cancer, immune function abnormality upon infection with HIV, immunefunction abnormality by stress, hemorrhagic stress, Cushing syndrome,thyroid function disorder, encephalomyelitis, acromegaly, incontinenceor osteoporosis.

[0212] The present invention provides a method for treating orpreventing diseases against which CRF and/or CRF receptor relate,diseases against which CRF receptor antagonism is efficacious,depressive symptoms such as depression, great depression, monostoticdepression, recurrent depression, infant tyrannism by depression,postpartum depression etc., mania, anxiety, generalized anxietydisorder, panic disorder, phobia, compulsive disorder, posttraumaticstress disorder, Tourette syndrome, autism, emotional disorder,sentimental disorder, bipolar disorder, cyclothymia, schizophrenia,peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'sdisease, diarrhea, coprostasis, postoperational ileus, gastrointestinalfunction abnormality associated with stress, neural vomiting, Alzheimerdisease, Alzheimer-type senile dementia, neurodegenerative disease,multi-infarct dementia, senile dementia, neurotic anorexia, dietdisorder, obesity, diabetes, alcohol dependence, pharmacophilia, drugabstinence symptoms, alcohol abstinence symptoms, sleep disorder,insomnia, migraine, stress headache, myotonic headache, ischemicneuropathy, excitation toxic neuropathy, cerebral apoplexy, progressivesupranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis,muscular convulsion, chronic fatigue syndrome, mental social growthfailure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodictorticollis, muscular convulsion, neck-shoulder-arm syndrome, primaryglaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis,hypertension, cardiovascular disorder, tachycardia, congestivecardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome,infant sudden death, syndrome, inflammatory disorder, pain, allergicdisease, impotence, climacteric disorder, fertilization disorder,infertility, cancer, immune function abnormality upon infection withHIV, immune function abnormality by stress, hemorrhagic stress, Cushingsyndrome, thyroid function disorder, encephalomyelitis, acromegaly,incontinence or osteoporosis, by administering a pharmacologicallyeffective dose of the compound represented by the above formula (I), apharmacologically acceptable salt thereof or hydrates thereof to apatient.

[0213] Further, the present invention provides use of the compoundrepresented by the above formula (I), a pharmacologically acceptablesalt thereof or hydrates thereof, for producing an agent for treating orpreventing diseases against which CRF and/or CRF receptor relate,diseases against which CRF receptor antagonism is efficacious,depressive symptoms such as depression, great depression, monostoticdepression, recurrent depression, infant tyrannism by depression,postpartum depression etc., mania, anxiety, generalized anxietydisorder, panic disorder, phobia, compulsive disorder, posttraumaticstress disorder, Tourette syndrome, autism, emotional disorder,sentimental disorder, bipolar disorder, cyclothymia, schizophrenia,peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'sdisease, diarrhea, coprostasis, postoperational ileus, gastrointestinalfunction abnormality associated with stress, neural vomiting, Alzheimerdisease, Alzheimer-type senile dementia, neurodegenerative disease,multi-infarct dementia, senile dementia, neurotic anorexia, dietdisorder, obesity, diabetes, alcohol dependence, pharmacophilia, drugabstinence symptoms, alcohol abstinence symptoms, sleep disorder,insomnia, migraine, stress headache, myotonic headache, ischemicneuropathy, excitation toxic neuropathy, cerebral apoplexy, progressivesupranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis,muscular convulsion, chronic fatigue syndrome, mental social growthfailure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodictorticollis, muscular convulsion, neck-shoulder-arm syndrome, primaryglaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis,hypertension, cardiovascular disorder, tachycardia, congestivecardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome,infant sudden death, syndrome, inflammatory disorder, pain, allergicdisease, impotence, climacteric disorder, fertilization disorder,infertility, cancer, immune function abnormality upon infection withHIV, immune function abnormality by stress, hemorrhagic stress, Cushingsyndrome, thyroid function disorder, encephalomyelitis, acromegaly,incontinence or osteoporosis.

[0214] The meanings of symbols, terms and the like described in thepresent specification will be explained below and the present inventionwill be explained in detail.

[0215] In the present specification, the structural formula of thecompound represents a certain isomer for convenience in some cases, butthe present invention includes all isomers such as geometrical isomer,optical isomer based on an asymmetrical carbon, stereoisomer, tautomerand the like which occur structurally and an isomer mixture and is notlimited to the description of the formula for convenience, and may beany one of isomer or a mixture. Therefore, an asymmetrical carbon atommay be present in the molecule and an optically active compound and aracemic compound may be present in the present compound, but the presentinvention is not limited to them and includes any one. In addition, acrystal polymorphism may be present but is not limiting, but any crystalform may be single or a crystal form mixture, or an anhydride orhydrate. Further, so-called metabolite which is produced by degradationof the present compound in vivo is included in the scope of the presentinvention.

[0216] The term ‘and/or’ in the present specification is used to includeboth the case of ‘and’ and case of ‘or’. Therefore, for example, ‘Aand/or B’ includes both the case of ‘A and B’ and the case of ‘A or B’and indicates that any case may be.

[0217] As used herein, ‘neural degenerative disease’ means acutedegenerative disease or chronic degenerative disease, specifically,means neural disorder derived from subarachnoidal hemorrhage,cerebrovascular disorder acute phase and the like, Alzheimer disease,Perkinson disease, Huntington's chorea, amyotrophic lateral sclerosis,spinal cerebellar degenerative disease and the like. As used herein,‘diet disorder’ means appetite sthenia, cibophobia and the like. As usedherein, ‘cardiovascular disorder’ means neural angina and the like. Asused herein, ‘inflammatory disorder’ menas, for example, rheumatoidarthritis, bone arthritis, lumbago and the like. ‘Allergy disease’denotes, for example, atopic dermatis, eczema, urticaria, psoriasis andthe like.

[0218] Meaning of A Group

[0219] ‘A group’ in ‘optionally substituted with any one or more groupslisted in A group’ used in the definition of each symbol in the aboveformula (I) means a group consisting of (1) halogen, (2) hydroxy group,(3) nitro group, (4) cyano group, (5) carboxyl group, (6) a C₁₋₆alkyloxycarbonyl group, (7) the formula —S(O)_(r)R¹³ (wherein r is aninteger of 0, 1 or 2; and R¹³ represents (i) hydorogen atom, (ii) a C₁₋₆alkyl group, (iii) the formula —NR¹⁴R¹⁵ (wherein R¹⁴ and R¹⁵ are thesame as or different from each other and each represents hydrogen atom,a C₁₋₆ alkyl group optionally substituted with an optionally substitutedaryl group, a C₁₋₄ alkylacy group, an optionally substituted aryl C₁₋₄alkyl group, an optionally substituted heteroaryl C₁₋₄ alkyl group, anoptionally substituted aryl group or an optionally substitutedheteroaryl group), (iv) an optionally substituted aryl C₁₋₄ alkyl group,(v) an optionally substituted aryl group, (vi) an optionally substitutedheteroaryl C₁₋₄ alkyl group or (vii) an optionally substitutedheteroaryl group), (8) —NR¹⁶R¹⁷ (wherein R¹⁶ and R¹⁷ are the same as ordifferent from each other and each represents hydrogen, a C₁₋₆ alkylgroup or a C₁₋₄ alkylacyl group), (9) a C₁₋₆ alkyl group, (10) a C₁₋₆alkoxy group, (11) a C₃₋₈ cycloalkyl group optionally substituted with aC₁₋₄ alkyl group, (12) a C₁₋₄ alkoxy C₁₋₆ alkyl group, (13) a saturated3- to 8-membered heterocyclic ring optionally substituted with a C₁₋₄alkyl group, (14) an optionally substituted aryl group and (15) anoptionally substituted heteroaryl group.

[0220] As a preferable atom in the above ‘halogen atom’, for example,fluorine, chlorine, bromine and iodine, more preferably fluorine,chlorine and bromine may be proposed.

[0221] ‘C₁₋₆ alkyl group’ in the above ‘C₁₋₆ alkyloxycarbonyl group’means an alkyl group having 1 to 6 of carbon number, and preferably aliner or branched alkyl group such as methyl group, etheyl group,n-propyl group, iso-propyl group, n-butyl group, iso-butyl group,sec-butyl group, tert-butyl group, n-pentyl group, 1,1-dimethylpropylgroup, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropylgroup, 2-ethylpropyl group, n-hexyl group, 1-methyl-2-ethylpropyl group,1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group,1-propylpropyl group, 1-methylbutyl group, 2-methylbutyl group,1-1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutylgroup, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutylgroup, 2-methylpentyl group and 3-methylpentyl group. Preferableexamples in the above ‘C₁₋₆ alkyloxycarbonyl group’ are carbonyl groupswith attached any C₁₋₆ alkyloxy group selected from methoxy group,ethoxy group, n-propoxy group, iso-propoxy group, sec-propoxy group,n-butoxy group, iso-butoxy group, sec-butoxy group, tert-butoxy group,n-pentyloxy group, iso-pentyloxy group, sec-pentyloxy group, n-hexoxygroup, iso-hexoxy group, 1,1-dimethylpropyloxy group,1,2-dimethylpropoxy, 2,2-dimethylpropyloxy group, 2-ethylpropoxy group,1-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy group,1,1,2-trimethylpropoxy group, 1,1-dimethylbutoxy group,1,2-dimethylbutoxy group, 2,2-dimethylbutoxy group, 2,3-dimethylbutyloxygroup, 1,3-dimethylbutyloxy group, 2-ethylbutoxy group,1,3-dimethylbutoxy group, 2-methylpentoxy group, 3-methylpentoxy group,hexyloxy group and the like.

[0222] ‘C₁₋₆ alkyl group’ in the definition of A group has the samemeaning of ‘C₁₋₆ alkyl group’ as defined above.

[0223] ‘C₁₋₄ alkyl group’ in the above ‘C₁₋₄ alkylacyl group’ representsan alkyl group having 1 to 4 of carbon number, and preferable example ofthe group are a group corresponding to an alkyl group having 1 to 4carbon number among groups listed in the above ‘C₁₋₆ alkyl group’.

[0224] ‘Aryl group’ in the above ‘optionally substituted aryl group’ or‘optionally substituted aryl C₁₋₄ alkyl group’ means ‘C₆₋₁₄ aromatichydrocarbon ring group’. As the preferable examples of the group,monocyclic, dicyclic or tricyclic C₆₋₁₄ aromatic hydrocarbon rings suchas phenyl group, indenyl group, 1-naphthyl group, 2-naphthyl group,azulenyl group, heptalenyl group, biphenyl group, indacenyl group,acenaphthyl group, fluorenyl group, phenalenyl group, phenanthrenylgroup, anthracenyl group, cyclopenta cyclooctenyl group andbenzocyclooctenyl group.

[0225] ‘Heteroaryl group’ in the above ‘optionally substitutedheteroalyl group’ or ‘an optionally substituted heteroaryl C₁₋₄ alkylgroup’ means ‘5- to 14-membered aromatic heterocyclic ring’ derived froma single ring or a fused ring, and preferable examples of the groupinclude (1) nitrogen-containing aromatic heterocyclic ring such aspyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group,pyrazinyl group, triazolyl group, tetrazolyl group, benzotriazolylgroup, pyrazolyl group, imidazolyl group, benzimidazolyl group, indolylgroup, isoindolyl group, indolizinyl group, purinyl group, indazolylgroup, quinolinyl group, isoquinolinyl group, quinolizinyl group,phthalazinyl group, naphthylidinyl group, quinoxalinyl group,quinazolinyl group, cinnolinyl group, pteridinyl group, imidazotriazinylgroup, pyrazinopyridazinyl group, acridinyl group, phenanthridinylgroup, carbazolyl group, carbazolinyl group, pyrimidinyl group,phenanthrolinyl group, phenacynyl group, imidazopyridinyl group,imidazopyrimidinyl group, pyrazolopyridinyl group and pyrazolopyridinylgroup; (2) sulfur-containing aromatic heterocyclic ring such as thienylgroup and benzothienyl group; (3) oxygen-containing aromaticheterocyclic ring such as furyl group, pyranyl group, cyclopentapyranylgroup, benzofuranyl group and isobenzofuranyl group; and (4) aromaticheterocyclic rings containing two or more heteroatoms selected fromnitrogen, sulfur and oxygen, such as thiazolyl group, isothiazolylgroup, benzothiazolyl group, benzthiadiazolyl group, phenothiazinylgroup, isoxazolyl group, furazanyl group, phenoxazinyl group, oxazolylgroup, benzooxazolyl group, oxadiazolyl group, pyrazolooxazolyl group,imidazothiazolyl group, thienofuranyl group, furopyrrolyl group andpyridoxazinyl group.

[0226] The preferable examples of the above ‘optionally substituted arylC₁₋₄ alkyl group’ include a C₁₋₄ alkyl group (for example, methyl group,ethyl group, n-propyl group, iso-propyl group, n-butyl group, iso-butylgroup, sec-butyl group, tert-butyl group and the like) substituted withan optionally substituted aryl group (for example, phenyl group, indenylgroup, 1-naphthyl group, 2-naphthyl group, azulenyl group, heptalenylgroup, biphenyl group, indacenyl group, acenaphthyl group, fluorenylgroup, phenalenyl group, phenanthrenyl group, anthracenyl group,cyclopentacyclooctenyl group, benzocyclooctenyl group and the like,which may be substituted, respectively), more preferably benzyl group,phenethyl group, naphthylmethyl group, naphthylethyl group and the like.In addition, the preferable examples of the above ‘optionallysubstituted heteroaryl C₁₋₄ alkyl group’ include a C₁₋₄ alkyl group (forexample, methyl group, ethyl group, n-propyl group, iso-propyl group,n-butyl group, iso-butyl group, sec-butyl group, tert-butyl group andthe like) substituted with an optionally substituted heteroaryl group(for example, pyrrolyl group, pyridyl group, pyridazinyl, pyrimidinylgroup, pyrazinyl group, thienyl group, thiazolyl group, furyl group andthe like which may be substituted, respectively), more preferablypyridylmethyl group, pyridylethyl group, thienylmethyl group,thienylethyl group and the like.

[0227] Examples of preferable groups in the above ‘C₁₋₆alkoxy group’ aremethoxy group, ethoxy group, n-propoxy group, iso-propoxy group,sec-propoxy group, n-butoxy group, iso-butoxy group, sec-butoxy group,tert-butoxy group, n-pentyloxy group, iso-pentyloxy group, sec-pentyloxygroup, n-hexoxy group, iso-hexoxy group, 1,1-dimethylpropyloxy group,1,2-dimethylpropoxy group, 2,2-dimethylpropyloxy group, 2-ethylpropoxygroup, 1-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy,1,1,2-trimethylpropoxy group, 1,1,2-trimethylpropoxy group,1,1-dimethylbutoxy group, 1,2-dimethylbutoxy group, 2,2-dimethylbutoxygroup,2,3-dimethylbutyloxy group, 1,3-dimethylbutyloxy group,2-ethylbutoxy group, 1, 3-dimethylbutoxy group, 2-methylpentoxy group,3-methylpentoxy group, hexyloxy group and the like.

[0228] ‘C₁₋₄ alkoxy group’ in the above ‘C₁₋₄ alkoxy C₁₋₆ alkyl group’means a group corresponding to an alkoxy group having 1 to 4 of carbonnumber among groups listed in the above ‘C₁₋₆alkoxy group’. Preferableexamples of ‘C₁₋₄ alkoxy C₁₋₆ alkyl group’ are C₁₋₆ alkyl groups (forexample, methyl group, ethyl group, n-propyl group, iso-propyl group,n-butyl group, iso-butyl group, sec-butyl group, tert-butyl group,n-pentyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group,2,2-dimethylpropyl group, 1-ethylpropyl group, 2-ethylpropyl group,n-hexyl group, 1-methyl-2-ethylpropyl group, 1-ethyl-2-methylpropylgroup, 1,1,2-trimethylpropyl group, 1-propylpropyl group, 1-methylbutylgroup, 2-methylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutylgroup, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group,2,3-dimethylbutyl group, 2-ethylbutyl group, 2-methylpentyl group,3-methylpentyl group and the like) in which the carbon atom issubstituted with any two or more groups selected from methoxy group,ethoxy group, n-propoxy group, i-propoxy group, sec-propoxy group,n-butoxy group, iso-butoxy group, sec-butoxy group, tert-butoxy groupand the like.

[0229] ‘C₃₋₈ cycloalkyl group’ in the above ‘C₃₋₈ cycloalkyl groupoptionally substituted with a C₁₋₄ alkyl group’ means a cycloalkyl groupin which 3 to 8 carbon atoms form a ring, and preferable examplesthereof include cyclopropyl group, cyclobutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclooctyl group and the like.

[0230] ‘Saturated 3- to 8-membered heterocyclic ring’ in the above‘saturated 3- to 8-membered heterocyclic ring optionally substitutedwith a C₁₋₄ alkyl group’ means a 3- to 8-membered saturated ringcontaining one or more heteroatoms selected from nitrogen, oxygen andsulfur, and preferable examples of the ring are aziridine, azetidine,pyrrolidine, piperidine, perhydroazepine, perhydroazocine, piperazine,homopiperazine, morpholine, thiomorpholine, tetrahydrofuran,tetrahydrothiopyran, perhydropyran, perhydrothiopyran, butyrolactone,butyrolactam and the like.

[0231] Preferable examples as the ‘substituent’ in the above ‘optionallysubstituted aryl’, ‘optionally substituted aryl group’, ‘optionallysubstituted heteroaryl’ or ‘optionally substituted heteroaryl group’,any one or more groups selected from (1) halogen atom (for example,fluorine atom, chlorine atom, bromine atom, iodine atom and the like);(2) hydroxy group; (3) thiol group; (4) nitro group; (5) cyano group;(6) a C₁₋₆ alkyl group, C₂₋₆ alkenyl group or C₂₋₆ alkynyl group whichmay be substituted with any one or more groups selected from a halogenatom and hydroxy group (for example, methyl, ethyl, n-propyl, isopropyl,fluoromethyl group, difluoromethyl group, trifluoromethyl group,2,2,2-trifluoroethyl group, hydroxymethyl group, hydroxyethyl group,hydroxypropyl group and the like) (7) a C₁₋₆ alkoxy group, C₂₋₆alkenyloxy group or C₂₋₆ alkynyloxy group which may be each substitutedwith a halogen atom or the like (for example, methoxy, ethoxy,n-propoxy, isopropoxy, butoxy group and the like); (8) a C₁₋₆ alkylthiogroup, C₂₋₆ alkenylthio group or C₂₋₆ alkynylthio group which may beeach substituted with halogen atom or the like (for example, methylthiogroup, ethylghio group, isopropylthio group and the like); (9) acylgroup (for example, acetyl group, propionyl group, benzoyl group and thelike); (10) amino group; (11) an amino group substituted with any 1 or 2groups selected from C₁₋₆ alkyl group, C₂₋₆ alkenyl group and C₂₋₆alkynyl group (for example, methylamino group, ethylamino group,isopropylamino group, dimethylamino group, diethylamino group and thelike); (12) cyclic amino group (for example, aziridinyl group,azetidinyl group, pyrrolidinyl group, piperidinyl group,perhydroazepinyl group, piperazinyl group and the like); (13) carboxylgroup; (14) a C₁₋₆ alkoxycarbonyl group, a C₂₋₆ alkenyloxycarbonyl groupor a C₂₋₆ alkynyloxycarbonyl group (for example, methoxycarbonyl group,ethoxycarbonyl group, propylcarbonyl group and the like); (15) carbamoylgroup optionally substituted with any group selected from a C₁₋₆ alkylgroup, a C₂₋₆ alkenyl group and a C₂₋₆ alkynyl group (for example,carbamoyl group, methylcarbamoyl group, dimethylcarbamoyl group and thelike); (16) acylamino group (for example, acetylamino group,benzoylamino group and the like); (17) sufamoyl group optionallysubstituted with any group selected from C₁₋₄ alkyl group, C₂₋₆ alkenylgroup and C₂₋₆ alkynyl group; (18) C₁₋₆ alkylsulfonyl group, C₂₋₆alkenylsulfonyl group or C₂₋₆ alkynylsulfonyl group (for example,methylsulfonyl group, ethylsulfonyl group and the like); (19) optionallysubstituted arylsulfonyl group (for example, benzenesulfonyl group,p-toluenesulfonyl group and the like); (20)optionally substituted arylgroup (phenyl group, tolyl group, anisolyl group and the like); (21)optionally substituted heteroaryl group (for example, pyrrole group,pyrazolyl group, imidazolyl group, triazolyl group, tetrazolyl group,thiazolyl group, pyridyl group, pyrimidyl group, pyrazinyl group and thelike); (22) C₁₋₆ alkyl group, C₂₋₆alkenyl group or C₂₋₆alkynyl groupsubstituted with carboxy group; (23) C₁₋₆ alkyloxycarbonyl C₁₋₆ alkylgroup (for example, methoxycarbonylmethyl group, ethoxycarbonylmethylgroup, methoxycarobonylethyl group and the like); (24) C₁₋₆alkoxy groupsubstituted with carboxyl group (for example, carboxymethoxy group andthe like); (25) C₁₋₆ alkyl group, C₂₋₆ alkenyl group or C₂₋₆ alkynylgroup substituted with aryl group (for example, benzyl group,4-chlorobenzyl group and the like); (25) C₁₋₆ alkyl group, C₂₋₆ alkenylgroup or C₂₋₆ alkynyl group substituted with heteroaryl group (forexample, pyridylmethyl group, pyridylethyl group and the like); (26)alkylenedioxy group (for example, methylenedioxy group, ethylenedioxygroup and the like); (27) optionally substituted C₃₋₈ cycloalkyl group;(28) optionally substituted C₃₋₈ cycloalkenyl group; and (29) optionallysubstituted 5- to 14-membered non-aromatic heterocyclic ring may beproposed.

[0232] Meaning of A, B and D

[0233] A, B and D in the above formula (I) are the same as or differentfrom each other and each represents (1) a heteroatom selected fromnitrogen atom, oxygen atom and sulfur atom; (2) —(CR¹R²)_(m)— (whereinR¹ and R² (i) are the same as or different from each other and eachrepresents hydrogen atom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, aC₂₋₆ alkynyl group, a C₁₋₆ alkoxy group, a C₃₋₈ cycloalkyl group, a C₁₋₆alkoxy C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl C₁₋₆ alkyl group or a C₁₋₆alkyl-aryl group, or R¹ and R² may be taken together to form a 3- to8-membered ring, (ii) R¹s are binded so that adjacent —CR¹R²-s form acarbon-carbon double bond, that is, the partial structure represented bythe formula —CR²═CR²—, or (iii) R¹ and nitrogen atom may form a bond sothat adjacent nitrogen atom and a group —CR¹R²— form the partialstructure represented by the formula —N═CR²— (R² is as defined above);and m means an integer from 0 to 4); (3) —CO—; (4) —CS—; (5) —NR³—(wherein R³ represents (i) hydrogen atom, (ii) formula —COR⁴ (wherein R⁴represents a C₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄ alkylgroup, an optionally substituted aryl group, an optionally substitutedheteroaryl C₁₋₄ alkyl group or an optionally substituted heteroarylgroup), (iii) —S(O)_(n)R⁵ (wherein R⁵ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group; and n means an integer of 0, 1or 2), (iv) a C₁₋₁₀ alkyl group optionally substituted with any one ormore groups listed in the following A group, (v) a C₂₋₁₀ alkenyl groupoptionally substituted with any one or more groups listed in thefollowing A group, (vi) a C₂₋₁₀ alkynyl group optionally substitutedwith any one or more groups listed in the following A group, (vii) anoptionally substituted aryl group or (viii) a C₃₋₈ cycloalkyl groupfused with an optionally substituted benzene ring, and optionallysubstituted with a C₁₋₄ alkyl group; (6) —SO—; or (7) —SO₂—.

[0234] (1) The above ‘C₁₋₆ alkyl group’ has the same meaning as ‘C₁₋₆alkyl group’ as defined in the A group. (2) The above ‘C₂₋₆ alkenylgroup’ means an alkenyl group having 2 to 6 of a carbon number, andpreferable examples of the group are linear or branched alkenyl groupssuch as vinyl group, allyl group, 1-propenyl group, 2-propenyl group,isopropenyl group, 2-methyl-1-propenyl group, 3-methyl-1-propenyl group2-methyl-2-propenyl group, 3-methyl-2-propenyl group, 1-butenyl group,2-butenyl group, 3-butenyl group, 1-pentenyl group, 1-hexenyl group,1,3-hexanedienyl group and 1,6-hexanedienyl group. Hereinafter, ‘C₂₋₆alkenyl group’ in the present specification has the same meaning asdefined above.

[0235] (3) The above ‘C₂₋₆ alkynyl group’ means an alkynyl group having2 to 6 of a carbon number, and preferable examples of the group arelinear or branched alkynyl groups such as ethynyl group, 1-propynylgroup, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynylgroup, 3-methyl-1-propynyl group, 1-ethynyl-2-propynyl group,2-methyl-3-propynyl group, 1-pentynyl group, 1-hexynyl group,13-hexanediynyl group and 1,6-hexanediynyl group. Hereinafter, ‘C₂₋₆alkynyl group’ in the present specification has the same meaning asdefined above.

[0236] ‘C₁₋₆ alkoxy group’, ‘C₃₋₈ cycloalkyl group’, ‘optionallysubstituted aryl C₁₋₄alkyl group’, ‘optionally substituted aryl group’,‘optionally substituted heteroaryl C₁₋₄ alkyl group’ and ‘optionallysubstituted heteroaryl group’ in the definition A, B and D have,respectively, the same meaning as ‘C₁₋₆ alkoxy group’, ‘C₃₋₈ cycloalkylgroup’, ‘optionally substituted aryl C₁₋₄ alkyl group’, ‘optionallysubstituted aryl group’, ‘optionally substituted heteroaryl C₁₋₄ alkylgroup’ and ‘optionally substituted heteroaryl group’ in the A group. Inaddition, the above ‘C₁₋₆ alkoxy C₁₋₆ alkyl group’ means ‘C₁₋₆ alkylgroup’ substituted with a group having the same meaning as ‘C₁₋₆ alkoxygroup’ in the above definition and, further, the above ‘C₃₋₈ cycloalkylC₁₋₆ alkyl group’ means ‘C₁₋₆ alkyl group’ substituted with a grouphaving the same meaning as ‘C₃₋₈ cycloalkyl group’ in the abovedefinition.

[0237] In the definition of A, B and D, ‘3- to 8-membered ring’ in ‘R¹and R² may be taken together to form a 3- to 8-membered ring’ means aC₃₋₈ carbocycle or heterocycle. The above ‘C₃₋₈ carbocycle’ means C₃₋₈cycloalkane, C₃₋₈ cycloalkene or C₃₋₈ cyclo alkyne, and the above‘heterocycle’ means a 3- to 8-membered ring containing any one or morehetero atoms selected from nitrogen atom, oxygen atom and sulfur atom.

[0238] (1) ‘C₁₋₁₀ alkyl group’ in the above ‘C₁₋₁₀ alkyl groupoptionally substituted with any one or more groups listed in A group’means an alkyl group having 1 to 10 of a carbon number. Preferableexamples of the group include, in addition to groups listed in ‘C₁₋₆alkyl group’ in the above definition, n-heptyl group, 1,2-dimethylpentylgroup, 2,3-dimethylpentyl group, 1,3-dimethylpentyl group,1-ethyl-2-methylbutyl group, 1-methyl-2-ethylbutyl group,1,2-diethylpropyl group, 2,3-diethylpropyl group, 1,3-diethylpropylgroup, 1-ethyl-2-propylethyl group, 1-propyl-2-methylpropyl group,1-propylbutyl group, n-octyl group, 1,2-dimethylhexyl group,2,3-dimethylhexyl group, 1,3-dimethylhexyl group, 1-ethyl-2-methylpentylgroup, 1-methyl-2-ethylpentyl group, 1,2-diethylbutyl group,2,3-dietylbutyl group, 1,3-diethylbutyl group, 1-ethyl-2-propylpropylgroup, 1-propyl-2-methylbutyl group, 1-butylbutyl group, n-nonyl group,1,2-dimethylheptyl group, 2,3-dimethylheptyl group, 1,3-dimethylheptylgroup, 1-ethyl-2-methylhexyl group, 1-methyl-2-ethylhexyl group,1,2-diethylpentyl group, 2,3-diethylpentyl group, 1,3-diethylpentylgroup, 1-ethyl-2-propylbutyl group, 1-propyl-2-methylpentyl group,1-propylhexyl group, 1-butylpentyl group, n-decanyl group,1,2-dimethyloctyl group, 2,3-demethyloctyl group, 1,3-dimethyloctylgroup, 1-ethyl-2-methylheptyl group, 1-methyl-2-ethylheptyl group,1,2-diethylhexyl group, 2,3-diethylhexyl group, 1,3-diethylhexyl group,1-ethyl-2-propylpentyl group, 1-propyl-2-methylhexyl group,1-propylheptyl group, 1-butylhexyl group, 1-pentylpentyl group and thelike. Hereinafter, ‘C₁₋₁₀ alkyl group’ in the present specification hasthe same meaning as defined above.

[0239] (2) ‘C₂₋₁₀ alkenyl group’ in the above ‘C₂₋₁₀ alkenyl groupoptionally substituted with any one or more groups listed in the Agroup’ means an alkenyl group having 2 to 10 of a carbon number, andpreferable groups for the group include linear or branched alkenylgroups such as vinyl group, allyl group, 1-propenyl group, 2-propenylgroup, isopropenyl group, 2-methyl-1-propenyl group, 3-methyl-1-propenylgroup, 2-methyl-2-propenyl group, 3-methyl-2-propenyl group, 1-butenylgroup, 2-butenyl group, 3-butenyl group, 1-pentenyl group, 1-hexenylgroup, 1,3-hexanedienyl group, 1,6-hexanedienyl group, 1-heptenyl group,1-octenyl group, 5-ethylenyl-1-hexenyl group, 1-nonenyl group and1-decenyl group. Hereinafter, ‘C₂₋₁₀ alkenyl group’ in the presentspecification has the same meaning as defined above.

[0240] (3) ‘C₂₋₁₀ alkynyl group’ in the above ‘C₂₋₁₀ alkynyl groupoptionally substituted with any one or more groups listed in the Agroup’ means an alkynyl group having 2 to 10 of a carbon number, andpreferable examples of the group include linear or branched alkynylgroups such as ethynyl group, 1-propynyl group, 2-propynyl group,1-butynyl group, 2-butynyl group, 3-butynyl group, 3-methyl-1-propynylgroup, 1-ethynyl-2-propynyl group, 2-methyl-3-propynyl group, 1-pentynylgroup, 1-hexynyl group, 1,3-hexanediynyl group, 1,6-hexanediynyl group,1-heptynyl group, 1-octynyl group, 5-ethylenyl-1-hexynyl group,1-nonyneyl group and 1-decynyl group. Hereinafter, ‘C₂₋₁₀ alkynyl group’in the present specification has the same meaning as defined above.

[0241] (4) As the most preferable group in the above ‘any one or moregroups listed in the A group’, a halogen atom, hydroxy group, a C₁₋₆alkoxy, ‘a C₃₋₈ cycloalxyl group optionally substituted with a C₁₋₄alkyl group’, ‘a saturated 3- to 8-membered heterocyclic ring optionallysubstituted with a C₁₋₄ alkyl group’, an optionally substituted arylgroup, and an optionally substituted heteroaryl group may be proposed.Respective groups have the same meanings as defined above for the sameterm, respectively, in the above ‘A group’.

[0242] ‘C₃₋₈ cycloalkyl group optionally fused with optionallysubstituted benzene ring, and optionally substituted with C₁₋₄ alkylgroup’ represented by R³ in the definition of A, B and D means ‘C₃₋₈cycloalkyl group’ optionally fused with ‘optionally substituted benzenering’ and further optionally substituted with ‘C₁₋₄ alkyl group’. The‘C₃₋₈ cycloalkyl group’ has the same meaning as defined above, and theexample of ‘C₃₋₈ cycloalkyl group optionally fused with optionallysubstituted benzene ring and optionally substituted with C₁₋₄ alkylgroup’ is 2,3-dihydroindenyl group.

[0243] As a preferable aspect of A, B and D in the compound representedby the above formula (I) relating to the present invention, there is acase where A, B and/or D are nitrogen atom, oxygen atom, sulfur atom, ora group represented by the formula —NR³— (wherein R³ has the samemeaning as defined above), CO—, —CS— or —(CR¹R²)_(m)— (wherein R¹, R²and m has the same meaning as defined above), more preferably the casewhere A, B and/or D are nitrogen, oxygen, sulfur, a group represented bythe formula —NR³— (wherein R³ has the same meaning as defined above)—CO—, —CS— or —(CR¹R²)_(m)— (wherein R¹ and R² have the same meanings asdefined above; and m′ represents an integer from 0 to 2). Morepreferably, there is the case where the partial structure represented bythe formula:

[0244] means a group represented by the formula:

—CH₂—CHR²—CHR²—; —CH₂—CHR²—NR³—; —CH═CR²—CHR²—

—CH₂—CHR²—O—; —CH₂—CHR²—S—; —CR²═N—NR³—

—CH═CR²—NR³—; —CR²═CR²—NR³—; —NH—CR²═CR²—

—N═CR²—CHR²—; —(CH₂)₂—CR²—NR³—; —(CH₂)₃—CR²—NR³—

—CH₂—CO—NR³—; —CO—NR³—CO—; —CO—NR³—NR³—

—NR³—CO—NR³—; —CH₂—CS—NR³—; —CS—NR³—CS—

—CS—NR³—NR³— or —NR³—CS—NR³—

[0245] wherein R²and R³, respectively, have the same meaning as definedabove, and R² and R³ represent the same or different groups. In such thecase, the most preferable groups in R² are hydrogen atom, methyl group,ethyl group, n-propyl group, iso-propyl group, n-butyl group, tert-butylgroup, n-pentyl group, 1-ethylpropyl group, methoxymethyl group,2-methoxyethyl group, 2-methoxy-n-propyl group, ethoxymethyl group,2-ethoxyethyl group, 2-ethoxy-n-propyl group, cyclopropylmethyl group,1-cyclopropylethyl group, 2-cyclopropylethyl group and the like, andexamples of the most preferable groups in R³ are (1) hydrogen atom, (2)a C₁₋₁₀ alkyl group, C₂₋₁₀ alkenyl group or C₂₋₁₀ alkynyl groupoptionally substituted with any one or more groups selected from hydroxygroup; a halogen atom; a C₁₋₆alkoxy group; an optionally substitutedC₃₋₈ cycloalkyl group; an optionally substituted aryl group; anoptionally substituted hetroaryl group; a mono C₁₋₆ alkyl-amino group; adi C₁₋₆ alkyl-amino group; and 3- to 5-membered saturated hetrocyclicring, (3) a C₁₋₆ alkylacyl group, (4) a C₁₋₆ alkylsulfonyl group and thelike. Respective groups have the same meanings as defined above.

[0246] Meaning of E, G, J, K and L

[0247] In the above formula (I),

[0248] E and G are the same as or different from each other and eachrepresents (1) a hetroatom selected from nitrogen atom, and oxygen atomand sulfur atom, (2) formula —(CR⁶R⁷)_(p) (wherein R⁶ and R⁷ (i) are thesame as or different from each other and each represetns hydrogen atom,a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group optionally substituted witha C₁₋₄ alkyl group, an optionally substituted aryl group or anoptionally substituted heteroaryl group, (ii) R⁶s are binded so thatadjacent —CR⁶R⁷-s form a carbon-carbon double bond, that is, the partialstructure represented by the formula —CR⁷═CR⁷— (wherein R⁷ has the samemeaning as defined above), or (iii) R⁶ and nitrogen atom may form a bondso that adjacent nitrogen atom and group —CR⁶R⁷— form the partialstructure represented by the formula —N═CR⁷— (R⁷ has the same meaning asdefined above); p means an integer of 0, 1 or 2, provided that, whenboth E and G are —(CR⁶R⁷)_(p)—, p does not mean 0; and at least one of Eand G represent —CR⁶R⁷—), (3) —CO—, (4) —CS—, (5) —NR⁸— (wherein R⁸represents (i) hydrogen atom, (ii) formula —COR⁹ (wherein R⁹ means aC₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄ alkyl group, anoptionally substituted aryl group, an optionally substituted hetroarylC₁₋₄ alkyl group or an optionally substituted heteroaryl group), (iii)—S(O)_(n)R¹⁰ (wherein R¹⁰ represents a C₁₋₆ alkyl group, an optionallysubstituted aryl C₁₋₄ alkyl group, an optionally substituted aryl group,an optionally substituted heteroaryl C₁₋₄ alkyl group or an optionallysubstituted heteroaryl group; and n means an integer of 0, 1 or 2), (iv)a C₁₋₁₀ alkyl group optionally substituted with any one or more groupslisted in the following A group, (v) a C₂₋₁₀ alkenyl group optionallysubstituted with any one or more groups listed in the following A group,(vi) a C₂₋₁₀ alkynyl group optionally substituted with any one or moregroups listed in the following A group, or (vii) a C₃₋₈ cycloalkyl groupoptionally fused with an optionally substituted benzene ring, andoptionally substituted with a C₁₋₄ alkyl group), (6) —SO—, or (7) —SO₂—;

[0249] J represents (1) nitrogen atom or (2) a carbon or nitrogen atomsubstituted with any one or more groups selected from the groupconsisting of (i) hydrogen atom, (ii) amino group, (iii) cyano, (iv) aC₁₋₆ alkyl group optionally substituted with a halogen atom, (v) a C₁₋₆alkylaminosulfonyl group, (vi) an optionally substituted aryl group and(vii) an optionally substituted saturated or unsaturated heterocyclicring; and

[0250] K and L are the same as or different from each other and eachrepresents carbon or nitrogen atom, respectively (provided that the casewhere both K and L are a nitrogen atom is excluded).

[0251] ‘C₁₋₄ alkyl group’, ‘C₁₋₆ alkyl group’, ‘C₃₋₈ cycloalkyl group’,‘optionally substituted aryl group’, ‘optionally substituted heteroarylgroup’, ‘optionally substituted aryl C₁₋₄ alkyl group’, ‘optionallysubstituted heteroaryl C₁₋₄ alkyl group’, ‘C₁₋₁₀ alkyl group optionallysubstituted with any one or more groups listed in the A group’, ‘C₂₋₁₀alkenyl group optionally substituted with any one or more groups listedin the A group’, ‘C₂₋₁₀ alkynyl group optionally substituted with anyone or more groups listed in the A group’ and ‘C₃₋₈ cycloalkyl groupoptionally fused with optionally substituted benzene group, andoptionally substituted with C₁₋₄ alkyl group’ in the definition of E andG respectively have the same meanings as those of ‘C₁₋₄ alkyl group’,‘C₁₋₆ alkyl group’, ‘C₃₋₈ cycloalkyl group’, ‘optionally substitutedaryl group’, ‘optionally substituted heteroaryl group’, ‘optionallysubstituted aryl C₁₋₄ alkyl group’, ‘optionally substituted heteroarylC₁₋₄ alkyl group’, ‘C₁₋₁₀ alkyl group optionally substituted with anyone or more groups listed in the A group’, ‘C₂₋₁₀ alkenyl groupoptionally substituted with any one or more groups listed in the Agroup’, ‘C₂₋₁₀ alkynyl group optionally substituted with any one or moregroups listed in the A group’ and ‘C₃₋₈ cycloalkyl group optionallyfused with optionally substituted benzene group, and optionallysubstituted with C₁₋₄ alkyl group’ described in the definition of theabove A group, A, B and D.

[0252] A preferable group in E and G is different depending upon anaspect of J and its substituent and K and L, and not particularlylimited but includes the same or different group represented by (1) aheteroatom selected from nitrogen atom, oxygen atom and sulfur atom, (2)the formula —(CR⁶R⁷)_(p)— (wherein R⁶, R⁷ and p have the same meaningsas defined above) or (3) —NR⁸— (where R⁸ has the same meaning as definedabove) More preferably, there is the case where the partial structure

E

G

is a group represented by the formula —(CHR⁷)₂—, —N═CR⁷—, —CR⁷═N—,—(CHR⁷)₃—, —CR⁷═CR⁷—CR⁷═, —N═CR⁷—CR⁷— or —CR⁷═CR⁷—N═ (wherein R⁷ has thesame meaning as defined above). In such the case, a more preferablegroup in R⁷ is also different depending upon an aspect of J and itssubstituent, and K and L are not particularly limited but includeshydrogen, a C₁₋₆ alkyl group (for example, methyl group, ethyl group,n-propyl group, isopropyl group, 1-ethyl-n-propyl group and the like), aC₃₋₈ cycloalkyl group (for example, cyclopropyl group, cyclobutyl group,cyclopentyl group, cyclohexyl group and the like), aryl group (forexample, phenyl group and the like), heteroaryl group (for example,pyridyl group, pyrimidinyl group, pyridazinyl group, pyrazinyl group,thienyl group, furyl group, imidazolyl group, thiazolyl group and thelike.

[0253] ‘Halogen atom’, ‘C₁₋₆ alkyl group’ and ‘an optionally substitutedaryl group’ in the definition of J have the same meanings as those of‘halogen atom’, ‘C₁₋₆ alkyl group’ and ‘an optionally substituted arylgroup’ described in the definitions of the above A group, A, B and D,respectively.

[0254] ‘C₁₋₆ alkylaminosulfonyl group’ in the definition of J means asulfonyl group substituted with ‘an amino group substituted with a C₁₋₆alkyl group’, and a preferable example includes methyl aminosulfonylgroup, ethylaminosulfonyl group, n-propylaminosulfonyl group,iso-propylaminosulfonyl group, n-butylaminosulfonyl group,tert-butylaminosulfonyl group and the like.

[0255] As a preferable group in J, for example, there is a carbon atomor nitrogen atom substituted with any one selected from (1) an arylgroup and (2) a saturated or unsaturated heterocyclic ring which may besubstituted, respectively. The above ‘aryl group’ has the same meaningas ‘aryl group’ in the above definition and, on the other hand,‘saturated or unsaturated heterocyclic ring’ represents morespecifically ‘5- to 14-membered non-aromatic heterocyclic ring’ or ‘5-to 14-membered aromatic heterocyclic ring’.

[0256] As a preferable ring in the above ‘5- to 14-membered non-aromaticheterocyclic ring’, for example, there are 5- to 14-memberedheterocyclic ring such as pyrrolidine, pyrroline, piperidine,piperazine, imidazoline, pyrazolidine, imidazolidine, morpholine,tetrahydrofuran, tetrahydropyran, aziridine, oxirane, oxathiolane,pyridone ring; unsaturated fused ring such as phthalimide ring andsuccinimide ring, and the like.

[0257] ‘5- to 14-membered aromatic heterocyclic ring’ means a ringcorresponding to a group listed in the above ‘heteroaryl’, and,preferably, pyrrole, pyridine, pyridazine, pyrimidine, pyrazine,pyrazole, imidazole, indole, isoindole, indolizine, purine, indazole,quinoline, isoquinoline, quinolizine, phthalazine, naphthyridine,quinoxaline, quinazoline, cinnoline, pteridine, imidazotriazine,pyrazinopyridazine, acridine, phenanthridine, carbazole, carbazoline,perimidine, phenanthroline, phenazine, thiophene, benzothiophene, furan,pyran, cyclopentapyran, benzofuran, isobenzofuran, thiazole,isothiazole, benzthiazole, benzthiadiazole, phenothiazine, isoxazole,furazane, phenoxazine, pyrazoloxazole, imidazothiazole, thienofuran,furopyrrole, pyridooxazine, 3-benzo[b]furan ring and the like.

[0258] Preferable examples of ‘aryl group’ or ‘heterocyclic ring’ in thecase where J is a carbon atom or nitrogen atom substituted with any onegroup selected from (1) an aryl group and (2) a saturated or unsaturatedheterocyclic ring which may be substituted, respectively, are phenylgroup and naphthyl group which may be substituted, respectively, andpyrrolidine, pyrroline, piperidine, piperazine, imidazoline, morpholine,tetrahydrofuran, pyridone, pyrrole, pyridine, pyridazine, pyrimidine,pyrazine, pyrazole, imidazole, indole, isoindole, thiophene,benzothiophene, furan, thiazole, isothiazole, benzthiazole,benzthiadiazole ring and the like which may be substituted,respectively. More preferable groups or rings are phenyl group, pyridinering, thiophene ring, furan ring and the like which may be substituted,respectively. Still preferable rings or groups are phenyl group andpyridine ring which may be substituted, respectively.

[0259] Preferable groups as ‘substituent’ in the above ‘optionallysubstituted aryl group’ or ‘optionally substituted saturated orunsaturated heterocyclic ring’ include, for example, one or more same ordifferent groups selected from (1) a halogen atom (for example, fluorineatom, chlorine atom, bromine atom and the like), (2) a C₁₋₆ alkyl groupoptionally substituted with a halogen atom (for example, methyl group,ethyl group, n-propyl group, iso-propyl group, trifluoromethyl group andthe like), (3) a C₁₋₆ alkoxy group (for example, methoxy group, ethoxygroup, n-propoxy group, iso-propoxy group and the like) and (4) an aminogroup optionally substituted with one or more linear hydrocarbon group(a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group and/or a C₂₋₆ alkynyl group)(for example, methylamino group, ethylamino group, dimethylamino group,diethylamino group, methylethylamino group and the like).

[0260] A preferable aspect in K and L is not particularly limited exceptfor the case where K and L are nitrogen atom, and includes the casewhere K and L are carbon atom, the case where K is carbon atom and L isnitrogen atom, and the case where L is nitrogen atom and L is carbonatom. The most preferable is the case where K is nitrogen atom and L iscarbon atom or the case where K and L are carbon atom.

[0261] A ring represented by the formula:

[0262] which is constituted by K, E, G, J and L in the above formula (I)represents an unsaturated 5- or 6-membered ring, and the ring may be ahydrocarbon ring or a heterocyclic ring containing a nitrogen atom. Asthe most preferable aspect in the ring, there is a ring represented bythe formula:

[0263] wherein R⁷ has the same meaning as defined above; and Wrepresents any one group selected from the group consisting of (i)hydrogen atom, (ii) amino group, (iii) cyano group, (iv) a C₁₋₆ alkylgroup optionally substituted with a halogen atom, (v) a C₁₋₆alkylaminosulfonyl group, (vi) an optionally substituted aryl group and(vii) an optionally substituted saturated or unsaturated heterocyclicring. Examples of preferable R⁷ in such the case are described for R⁷ asdefined above. In addition, examples of preferable W are an optionallysubstituted aryl group and saturated or unsaturated heterocyclic ring.And preferable examples of the group or ring are as defined forsubstituents of J in the above definition. Provided that, in theforegoing, the case where K is nitrogen, L is carbon, A and B are agroup represented by the formula —(CR¹R²)_(m)— (wherein both R¹ and R²represents hydrogen; and m is 1), respectively, and J is a carbonsubstituted with any group selected from (i) amino group; (ii) cyanogroup; (iii) an aminosulfonyl group in which the nitrogen atom issubstituted with a linear or branched C₁₋₆ alkyl group; and (iv)1H-tetrazol-5-yl group, is excluded.

[0264] Meaning of M

[0265] In the above formula (I), M represents (1) hydrogen atom, (2) ahalogen atom, (3) cyano group, (4) a C₁₋₆ alkyl group optionallysubstituted with any one or more groups listed in the above A group, (5)the formula —NR¹¹R¹²— (wherein R¹¹ and R¹² are the same as or differentfrom each other and each represents (i) hydrogen atom, (ii) any grouplisted in the following A group, (iii) a C₁₋₆ alkyl group optionallysubstituted with any one or more groups listed in the following A group,(iv) a C₁₋₄ alkylacyl group, (v) an optionally substituted aryl C₁₋₄alkyl group, (vi) an optionally substituted heteroaryl C₁₋₄ alkyl group,(vii) an optionally substituted aryl group or (viii) an optionallysubstituted heteroaryl group), (6) —OR¹¹ (where R¹¹ represents hydrogenatom, a C₁₋₆ alkyl group optionally substituted with any one or moregroups listed in the above A group, a C₁₋₄ alkylacyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedheteroaryl C₁₋₄ alkyl group, an optionally substituted aryl group or anoptionally substituted heteroaryl group), (7) —S(O)_(q)R¹² (wherein R¹²represents a C₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄ alkylgroup, an optionally substituted aryl group, an optionally substitutedheteroaryl C₁₋₄ alkyl group, an optionally substituted aryl group, anoptionally substituted heteroaryl C₁₋₄ alkyl group or an optionallysubstituted heteroaryl group; q means an integer of 0, 1 or 2), (8) anoptionally substituted C₂₋₁₀ alkenyl group, (9) an optionallysubstituted C₂₋₁₀ alkynyl group, (10) a C₁₋₆ alkoxy group optionallysubstituted with one or more groups listed in the following A group,(11) a C₁₋₆ alkylthio group optionally substituted with one or moregroups listed in the following A group, (12) an optionally substitutedaryl group or (13) an optionally substituted heteroaryl group.

[0266] ‘Halogen atom’, ‘C₁₋₆ alkyl group’, ‘C₁₋₄ alkylacyl group’, ‘anoptionally substituted aryl C₁₋₄ alkyl group’, ‘an optionallysubstituted heteroaryl C₁₋₄ alkyl group’, ‘an optionally substitutedaryl group’, ‘an optionally substituted heteroaryl group’, ‘C₂₋₁₀alkenyl group’, ‘C₂₋₁₀ alkynyl group’ and ‘C₁₋₆ alkoxy group’ in thedefinition of M have, respectively, the same meanings as those of‘halogen atom’, ‘C₁₋₆ alkyl group’, ‘C₁₋₄ alkylacyl group’, ‘anoptionally substituted aryl C₁₋₄ alkyl group’, ‘an optionallysubstituted heteroaryl C₁₋₄ alkyl group’, ‘an optionally substitutedaryl group’, ‘an optionally substituted heteroaryl group’, ‘a C₂₋₁₀alkenyl group’, ‘C₂₋₁₀ alkynyl group’ and ‘C₁₋₆ alkoxy group’ describedin the above definitions of A group, A, B and D.

[0267] Preferable groups in ‘C₁₋₆ alkylthio group’ in the definition ofM are methylthio group, ethylthio group, n-propyl group, iso-propylthiogroup, n-butylthio group, iso-butylthio group, sec-butylthio group,tert-butylthio group, n-pentylthio group, 1,1-dimethylpropylthio group,1,2-dimethylpropylthio group, 2,2-dimethylpropylthio group,1-ethylpropylthio group, 2-ethylpropylthio group, n-hexylthio group,1-methyl-2-ethylpropylthio group, 1-ethyl-2-methylpropylthio group,1,1,2-trimethylpropylthio group, 1-propylpropylthio group,1-methylbutylthio group, 2-methylbutylthio group, 1,1-dimethylbutylthiogroup, 1,3-dimethylbutylthio group, 2,3-dimethylbutylthio group,2-ethylbutylthio group, 2-methylpentylthio group, 3-methylpentylthiogroup and the like. More preferred are methylthio group, ethylthiogroup, n-propylthio group, iso-propylthio group, n-butylthio group,iso-butylthio group, sec-butylthio group and tert-butylthio group.

[0268] Preferable groups in M are not particularly limited, but examplesof more preferred are a halogen atom (for example, fluorine, chlorine,bromine and the like), a C₁₋₆ alkyl group optionally substituted withany one or more groups selected from the above A group, the formula—NR⁹R¹⁰— (wherein R⁹ and R¹⁰ are the same as or different from eachother and each represents hydrogen, a C₁₋₆ alkyl group optionallysubstituted with any one or more groups listed in the above A group, aC₁₋₄ alkylacyl group, an optionally substituted aryl C₁₋₄ alkyl group,an optionally substituted heteroaryl C₁₋₄ alkyl group, an optionallysubstituted aryl group or an optionally substituted heteroaryl group),an optionally substituted C₂₋₁₀ alkenyl group, an optionally substitutedC₂₋₁₀ alkynyl group and the like. Still preferable groups in M are ahalogen atom (for example, fluorine, chlorine, bromine and the like), aC₁₋₆ alkyl group, a C₂₋₁₀ alkenyl group, a C₂₋₁₀ alkynyl group and thelike, and the most preferred are a halogen atom, methyl group, ethylgroup, n-propyl group, iso-propyl group and the like.

[0269] An aspect of the compound represented by the above formula (I)relating to the present invention is not particularly limited, and aperson in the art can arbitrarily combine groups listed regarding A, B,D, E, G, J, K, L and M in the above definition and implement allcompounds in the range. Among them, a more preferable aspect is, forexample, a compound represented by the formula:

[0270] (wherein A, B, K, E, G, J, L and R³ have the same meanings asdefined above; M′ represents halogen atom, a C₁₋₆ alkyl group optionallysubstituted with any one or more groups selected from the above A group,the formula —NR⁹R¹⁰— (wherein R⁹ and R¹⁰ have the same meanings asdefined above), an optionally substituted C₂₋₁₀ alkenyl group or anoptionally substituted C₂₋₁₀ alkynyl group; W represents hydrogen atom,amino group, cyano group, a C₁₋₆ alkyl group, a C₁₋₆ alkylaminosufonylgroup, an optionally substituted aryl group or an optionally substitutedsaturated or unsaturated heterocyclic ring), a salt thereof or hydratesthereof. A still preferable aspect is a compound represented by theformula:

[0271] (wherein M′, R² and R³ have the same meanings as defined above;R⁷′ represents hydrogen or a C₁₋₆ alkyl group; and W′ represents anoptionally substituted aryl group or an optionally substituted saturatedor unsaturated heterocyclic ring), a salt thereof or hydrates thereof.

[0272] As an specific embodiment in a compound relating to the presentinvention, there are the following suitable compounds:

[0273]8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0274]8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0275]3-mesityl-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0276]8-benzyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0277]3-mesityl-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0278]3-mesityl-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0279]2-ethyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0280]8-(1-ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethyl-3-pyridyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;

[0281] 6-mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine;

[0282]9-(cyclopropylmethyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine;

[0283] 2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-yl)butyl methylether;

[0284]1-(1-ethylpropyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridine;and

[0285]2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,5]naphthyridine-1-yl)butylmethyl ether.

[0286] ‘Pharmacologically acceptable salt’ in the present specificationis not particularly limited as long as it forms a salt with a compoundof the present invention and pharmacologically acceptable. Preferableexamples include hydrogen halide salts (for example, hydrofluoride,hydrochloride, hydrobromide, hydroiodide and the like), inorganic acidsalts (for example, sulfate, nitrate, perchlorate, phosphate, carbonate,bicarbonate and the like), organic acid salts (for example, acetate,trifluoroacetate, oxalate, maleate, tartate, fumarate, citrate and thelike), organic sulfonic acid salts (for example, methanesulfonate,trifluoromethanesulfonate, ethanesulfonate, benzenesulfonate,camphorsulfonate and the like), amino acid salts (for example,aspartate, glutamate and the like), quaternary amine salt, alkali metalsalts (for example, sodium salt, potassium salt and the like), alkalineearth metal salts (magnesium salt, calcium salt and the like) and thelike. As the ‘pharmacologically acceptable salt’, more preferred arehydrochloride, oxalate, trifluoroacetate and the like.

[0287] A representative process for preparing the compound according tothe present invention represented by the above formula (I) will bedescribed below.

[0288] (1) A compound (I-1) wherein D is a nitrogen atom in a compoundaccording to the present invention represented by the above formula (I)can be prepared via steps 1-A to E shown in the formula:

[0289] wherein R¹, R² and R⁷ have the same meanings as defined above;R³′ represents hydrogen atom, a C₁₋₁₀ alkyl group optionally substitutedwith any one or more groups listed in the above A group, a C₂₋₁₀ alkenylgroup optionally substituted with any one or more groups listed in theabove A group, a C₂₋₁₀ alkynyl group optionally substituted with any oneor more groups listed in the above A group or a C₃₋₈ cycloalkyl groupoptionally fused with an optionally substituted benzene ring andoptionally substituted with a C₁₋₄ alkyl group;

[0290] R³ represents a C₁₋₆ alkyl group; X represents chlorine, bromineor iodine; W represents hydrogen atom, amino group, cyano group, a C₁₋₆alkyl group, a C₁₋₆ alkylaminosulfonyl group, an optionally substitutedaryl group or an optionally substituted saturated or unsaturatedheterocyclic ring; M¹ represents a C₁₋₆ alkyl group optionallysubstituted with any one or more groups listed in the above A group, anoptionally substituted aryl group or an optionally substitutedheteroaryl group; and s means an integer from 1 to 4.

[0291] A compound (3) can be obtained by reacting acetonitrile compound(1) with a compound (2) at −78 to 200° C. in the presence of a base in asolvent (Step 1-A). A base used is different depending upon a startingraw material, the solvent used and the like, and is not particularlylimited as long as it dose not inhibit the reaction. Preferably, aminessuch as triethylamine, diisopropylamine, N,N-diisopropylethylamine,N,N-diisopropylethylamine and pyridine; inorganic salts such as sodiumcarbonate, potassium carbonate and sodium bicarbonate; alcoholates suchas sodium methoxide, sodium ethoxide and potassium tert-butoxide; metalamides such as sodium amide and lithium diisopropylamide; metal hydridessuch as sodium hydride, potassium hydride and calcium hydride etc. maybe proposed. A solvent used is different depending upon a starting rawmaterial, a reagent and the like, and is not particularly limited aslong as it dose not inhibit the reaction and dissolves a startingmaterial to some extent. Suitable solvents are alcohols such asmethanol, ethanol, isopropylalcohol and ethylene glycol; ethers such asdiethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane;hydrocarbons such as benzene and toluene; amides such asN,N-dimethylformamide; acetonitrile; water, or a mixed solvent of them.

[0292] An aminopyrazole derivative (5) can be obtained by reacting acompound (3) and hydrazine hydrate (4) at 0 to 200° C. in the presenceor absence of an acid in a solvent (Step 1-B). An acid used is differentdepending upon a raw material, a reagent, the solvent used and the like,and is not particularly limited as long as it dose not inhibit thereaction. Suitable acids are inorganic acids such as hydrochloric acid,hydrobromic acid and sulfuric acid; organic acids such asp-toluenesulfonic acid, methanesulfonic acid, acetic acid andtrifluoroacetic acid. A solvent used is different depending upon a rawmaterial, a reagent used and the like, and is not particularly limitedas long as it dose not inhibit the reaction and dissolves a raw materialto some extent. Suitable solvents are alcohols such as methanol,ethanol, isopropylalcohol and ethylene glycol; ethers such as diethylether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane; hydrocarbonssuch as benzene and toluene; amides such as N,N-dimethylformamide;acetonitrile; water, or a mixed solvent thereof.

[0293] Pyrazolo[1,5-a]pyrimidine derivative (8) can be obtained byreacting am aminopyrazole derivative (5) and an acyllactone derivative(6) at 0 to 200° C. in the presence or absence of an acid in a solvent(Step 1-C). An acid used is different depending upon a raw materialused, a reagent, the solvent and the like to be used, and is notparticularly limited as long as it dose not inhibit the reaction.Suitable acids are inorganic acids such as hydrochloric acid,hydrobromic acid and sulfuric acid; and organic acids such asp-toluenesulfonic acid, methanesulfonic acid, acetic acid andtrifluoroacetic acid. A solvent used is different depending upon a rawmaterial used, a reagent and the like to be used, and is notparticularly limited as long as it dose not inhibit the reaction anddissolves a raw material to some extent. Preferably, alcohols such asmethanol, ethanol, isopropyl alcohol and ethylene glycol; ethers such asdiethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane;hydrocarbons such as benzene, toluene and xylene; amides such asN,N-dimethylformamide; acetonitrile; water, or a mixed solvent of themetc. may be proposed. Pyrazoloaminomethylenelactone (7) is precipitatedduring the present reaction is some cases but isolation and heating in asolvent again afford (8).

[0294] A dihalogeno compound (9) can be obtained in one stage or twostage reaction by reacting a compound (8) and a halogenating agent at−80 to 250° C. in the presence or absence of a base and in the presenceor absence of a quaternary salt in a solvent or without a solvent (Step1-D). A halogenating agent, a base and a quaternary salt used aredifferent depending upon a raw material, a reagent and the solvent used.Preferable examples of a halogenating agent are thionyl chloride,phosphorus oxychloride, phosphorus trichloride, phosphoruspentachloride, phosphorus oxybromide, phosphorus tribromide, phosphoruspentabromide, oxalyl chloride and the like. Preferable bases aretriethylamine, diisopropylamine, N,N-diisopropylethylamine,N,N-diisopropylethylamine, pyridine, dimethylaniline, diethylaniline andthe like. Preferable quaternary salts are tetraethylammonium chloride,tetraethylammonium bromide, triethylmethylammonium chloride,triethylmethylammonium bromide and the like. A solvent used is differentdepending upon a raw material, a reagent and the like to be used, and isnot particularly limited as long as it dose not inhibit the reaction anddissolves a raw material to some extent. Suitable solvents are etherssuch as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane;and hydrocarbons such as benzene, toluene and xylene, or a mixed solventof them.

[0295] A pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine (I-1) of the presentinvention can be obtained by adding an amine derivative (10) to adihalogeno compound (9) in a solvent or without a solvent (Step 1-E).When the reaction is performed in a solvent, such the solvent isdifferent depending upon a raw material, a reagent and the like to beused, and is not particularly limited as long as it dose not inhibit thereaction and dissolves a raw material to some extent. Preferably,alcohols such as methanol, ethanol, isopropyl alcohol and ethyleneglycol; ethers such as diethyl ether, tetrahydrofuran, dioxane and1,2-dimethoxyethane; hydrocarbons such as benzene, toluene and xylene;amides such as N,N-dimethylformamide; alkylnitriles such asacetonitrile; ketones such as methyl ethyl ketone; a mixed solvent ofthem etc. may be proposed. The present reaction is conducted in thepresence or absence of a base and, when a base is used, such the base isdifferent depending upon raw material, other reagents to be used, and isnot particularly limited. Preferably, amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine, N,N-diisopropylethylamineand pyridine; inorganic salts such as sodium carbonate, potassiumcarbonate and sodium bicarbonate; alcoholates such as sodium methoxide,sodium ethoxide and potassium tert-butoxide; metal amides such as sodiumamide and lithium diisopropylamide; metal hydrides such as sodiumhydride, potassium hydride and calcium hydride etc. may be proposed. Inaddition, an amine (10) which is a reaction reagents may be also used abase by using it an excessive amount. A reaction temperature is usually−80 to 250° C.

[0296] Regarding the above Preparation method 1, a compound wherein thering constituted by A, B and D in the above formula (I) is 6- or7-membered ring can be prepared as follows;

[0297] A compound (9″) can be obtained by adding an amine derivative(10) to a dihalogeno compound (9′) in an inert solvent or withoutsolvent (step1′-C). An inert solvent used is different depending upon araw material, a reagents and the like to be used, and is notparticularly limited as long as it does not inhibit the reaction anddesolves a raw material to some extent. Preferably, xylene, toluene,benzene, tetrahydrofuran, N-methylpyrrolidone, N,N-dimethylformamide,1,4-dioxane, dimethoxyethane, ethanol, acetonitrile etc. may beproposed. Alternatively, an amine (10) which is a raw material may beused as a solvent. A reaction temperature is usually a room temperatureto the boiling point of the solvent.

[0298] A pyrozolo[1,5-a]pyrrolo[3,2-e]pyrimidine compound (I-1′) of thepresent invention can be obtained by cyclizing intramolecularly thecompound (9″) prepared in Step 1′-C (Step 1′-D). A reaction solvent useddifferent depending upon a raw material, a reagents and the like to beused, and is not particularly limited as long as it does not inhibit thereaction and dissolves a starting material to some extent. Suitablereaction solvents are tetrahydrofuran, N-methylpyrrolidone,N,N-dimethylformamide, dimethylsulfoxide, 1,4-dioxane, dimethoxyethane,ethanol, acetonitrile and the like. It is preferable that the presentreaction can be performed by adding a base (for example, triethylamine,pyridine, potassium carbonate and the like) and the better results canbe obtained. Alternatively, the addition of sodium iodide as a catalystto the reaction system is also a preferable method. A reactiontemperature is usually room temperature to the boiling point of thesolvent.

[0299] Although a commercial derivative can be usually used as lactone(6) used in the above Step 1-C, when substituents are introduced toparts of R¹ and R² of (6), the lactone may be also prepared by an easymethod by a person skilled in the art as follows:

[0300] The reaction is usually performed in the presence or absence of abase in an inert solvent. An inert solvent used is different dependingupon a raw material, a reagent and the like to be used, and is notparticularly limited as long as it does not inhibit the reaction anddissolves a starting materials to some extent. Suitable inert solventsare xylene, toluene, benzene, tetrahydrofuran, N-methylpyrrolidone,N,N-dimethylformamide, 1,4-dioxane, 1,2-dimethoxyethan, methanol,acetonitrile and the like. A base used is different depending upon astarting material, a reagent, the solvent and the like, and is notparticularly limited. Suitable bases are sodium hydride, sodiummethoxide, sodium t-butoxide, lithium diisopropylamide, butylrithium andthe like. A reaction temperature is usually room temperature to theboiling point of the solvent.

[0301] A compound of the present invention can be prepared using as astarting raw material the above aminopyrazole derivative (5) by anothermethod different from a preparation method 1 that is, a methodrepresented by the formula:

[0302] wherein R¹, R², R³′, R⁷, W, M¹, X and s have the same meanings asdefined above; R^(b) and R^(c) are the same as or different from eachother and each represents a C₁₋₆ alkyl group.

[0303] First, a pyrazolo[1,5-a]pyrimidine derivative (12) which is anintermediate can be prepared by reacting a compound (5) and a compound(11) at 0 to 200° C. in the presence or absence of an acid in an inertsolvent (Step 2-A). An acid used is different depending upon a rawmaterial, other reagents, the solvent and the like to be used, and isnot particularly limited. Suitable acids are inorganic acids such ashydrochloric acid, hydrobromic acid and sulfuric acid; and organic acidssuch as p-toluenesulfonic acid, methanesulfonic acid, acetic acid andtrifluoroacetic acid. Preferable examples in an inert solvent used arealcohols such as methanol, ethanol, isopropyl alcohol and ethyleneglycol; ethers such as diethyl ether, tetrahydrofuran, dioxane and1,2-dimethoxyethan; hydrocarbons such as benzene, toluene and xylene;amides such as N,N-dimethylformamide; acetonitrile; water, or a mixedsolvent of them.

[0304] A compound (13) can be obtained by reacting a compound (12) and ahalogenating reagent in the presence or absence of a base, and in thepresence or absence of a quaternary salt in an inert solvent or withouta solvent (Step 2-B). A halogenating agent, a base and a quaternary saltto be used are different depending upon a raw material, a reagent, thesolvent and the like to be used. Preferable examples of the halogenatingagent are thionyl chloride, phosphorus oxychloride, phosphorustrichloride, phosphorus pentachloride, phosphorus oxybromide, phosphorustribromide, phosphorus pentabromide, oxalylchloride and the like.Preferable examples of the base are amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine, pydidine, dimethylanilineand diethylaniline; in organic salts such as sodium carbonate, potassiumcarbonate and sodium bicarbonate; alcoholates such as sodium methoxide,sodium ethoxide and potassium tert-butoxide; metal amides such as sodiumamide and lithium diisopropylamide; metal hydrides such as sodiumhydride, potassium hydride and calcium hydride, and the like. Preferablequaternary salts are tetraethylammonium chloride, tetraethylammoniumbromide, triethylmethylammonium chloride, triethylmethylammonium bromideand the like. An inert solvent used is different depending upon a rawmaterial, a reagent and the like to be used, and is not particularlylimited as long as it does not inhibit the reaction and dissolves astarting material to some extent. Preferably, alcohols such as methanolethanol, isopropyl alcohol and ethylene glycol; ethers such as diethylether, tetrahydrofuran, dioxane and 1,2-dimethoxyethan; hydrocarbonssuch as benzene, toluene and xylene; amides such asN,N-dimethylformamide; acetonitrile; water, or a mixed solvent of themmay be proposed.

[0305] A pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine derivative (I-2) of thepresent invention can be obtained by reacting a compound (13) and aprimary amine (10) at −80 to 250° C. in the presence or absence of abase in a solvent or without a solvent (Step 2-C). A base used isdifferent depending upon a raw material, a reagent, the solvent and thelike to be used. Preferably, amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine and pydidine; inorganicsalts such as sodium carbonate, potassium carbonate and sodiumbicarbonate; alcoholates such as sodium methoxide, sodium ethoxide andpotassium tert-butoxide; metal amides such as sodium amide and lithiumdiisopropylamide; metal hydrides such as sodium hydride, potassiumhydride and calcium hydride may be proposed. Amine (10) which is areaction reagent may be also acted as a base in the present reaction. Aninert solvent to be used is different depending upon a raw material, areagent and the like to be used, and is not particularly limited as longas it does not inhibit the reaction and dissolves a starting a materialto some extent. Preferably, alcohols such as methanol ethanol, isopropylalcohol and ethylene glycol; ethers such as diethyl ether,tetrahydrofuran, dioxane and 1,2-dimethoxyethan; hydrocarbons such asbenzene, toluene and xylene; amides such as N,N-dimethylformamide;alkylnitriles such as acetonitrile; ketones such as methyl ethyl ketone;water, or a mixed solvent of them may be proposed.

[0306] A compound wherein D is nitrogen atom, and A and B are a grouprepresented by the formula —CO— in a compound represented by the aboveformula (I) of the present invention can be obtained by a methodrepresented by the formula:

[0307] wherein R^(a), R^(d), J, W, M¹, R″, X and s have the samemeanings as defined above.

[0308] A pyrazolo[1,5-a]pyrimidine derivative (15) can be obtained byreacting a compound (5) and a compound (14) at −80 to 300° C. in thepresence or absence of a base in a solvent or without a solvent (Step3-A). A base used is different depending upon a starting raw material, areagent, the solvent and the like to be used, and is not particularlylimited. Preferably, amines such as triethylamine, diisopropylamine,N,N-diisopropylethylamine and pyridine; inorganic salts such as sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonateand sodium bicarbonate; alcoholates such as sodium methoxide, sodiumethoxide and potassium tert-butoxide; metal amides such as sodium amide,lithium diisopropylamide, lithium bis(trimethylsilyl)amide; metalhydrides such as sodium hydride, potassium hydride and calcium hydride;organic magnesium compounds such as methylmagnesium bromide andethylmagnesium bromide; organic lithium compounds such as butyllithiumand methyllithium may be proposed. An inert solvent used is differentdepending upon a raw material, a reagent and the like to be used, and isnot particularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Preferably, alcohols suchas methanol ethanol, isopropyl alcohol and ethylene glycol; ethers suchas diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethan anddiphenyl ether; hydrocarbons such as benzene, toluene and xylene; amidessuch as N,N-dimethylformamide and 1-methyl-2-pyrrolidinone;alkylnitriles such as acetonitrine; ketones such as methyl ethyl ketone;water, and a mixed solvent of them may be proposed.

[0309] An intermediate (16) can be obtained by reacting a compound (15)and a halogenating reagent at −80 to 250° C. in the presence or absenceof a base and in the presence or absence n a quaternary salt in asolvent or without a solvent (Step 3-B). A halogenating agent, a baseand a quaternary salt to be used are different depending upon a startingraw material, a reagent, the solvent and the like, and are notparticularly limited. Preferable examples of the halogenating agent arethionyl chloride, phosphorus oxychloride, phosphorus trichloride,phosphorus pentachloride, phosphorus oxybromide, phosphorus tribromide,phosphorus pentabromide, oxalyl chloride and the like. Suitable examplesof the base are amines such as triethylamine, diisopropylamine,N,N-diisopropylethylamine, pydidine, dimethylaniline and diethylaniline;inorganic salts such as sodium carbonate, potassium carbonate and sodiumbicarbonate; alcoholates such as sodium methoxide, sodium ethoxide andpotassium tert-butoxide; metal amides such as sodium amide and lithiumdiisopropylamide; metal hydrides such as sodium hydride, potassiumhydride and calcium hydride. Preferable examples of a quaternary saltare tetraethylammonium chloride, tetraethylammonium bromide,triethylmethylammonium chloride, triethylmethylammonium bromide and thelike. An inert solvent used is different depending upon a raw material,a reagent and the like to be used, and is not particularly limited aslong as it does not inhibit the reaction and dissolves a startingmaterial to some extent. Suitable are alcohols such as methanol ethanol,isopropyl alcohol and ethylene glycol; ethers such as diethyl ether,tetrahydrofuran, dioxane and 1,2-dimethoxyethane; hydrocarbons such asbenzene, toluene and xylene; amides such as N,N-dimethylformamide;acetonitrile; water, or a mixed solvent of them.

[0310] An aminopyrimidine derivative (17) can be obtained by reacting acompound (16) and a primary amine (10) at −80 to 250° C. in the presenceor absence of a base in a solvent or without a solvent (Step 3-C). Abase used is different depending upon a starting raw material, areagent, the solvent and the like, and is not particularly limited.Suitable are amines such as triethylamine, diisopropylamine,N,N-diisopropylethylamine and pydidine; inorganic salts such as sodiumcarbonate, potassium carbonate and sodium bicarbonate; alcoholates suchas sodium methoxide, sodium ethoxide and potassium tert-butoxide; metalamides such as sodium amide and lithium diisopropylamide; metal hydridessuch as sodium hydride, potassium hydride and calcium hydride.Alternatively, amine (10) which is a reaction reagent may be acted asthe base. A solvent used is different depending upon a raw material, areagent and the like to be used, and is not particularly limited as longas it does not inhibit the reaction and dissolves a starting material tosome extent. Suitable are alcohols such as methanol ethanol, isopropylalcohol and ethylene glycol; ethers such as diethyl ether,tetrahydrofuran, dioxane and 1,2-dimethoxyethane; hydrocarbons such asbenzene, toluene and xylene; amides such as N,N-dimethylformamide;alkylnitriles such as acetonitrile; ketons such as methyl ethyl keton;water, or a mixed solvent of them.

[0311] A carboxylic acid (18) can be obtained by hydrolyzing an ester(17) at 0 to 200° C. in the presence of an acid or a base in a solvent(Step3-D). An acid used is different depending upon a starting rawmaterial, a reagent, the solvent and the like, and is not particularlylimited. Suitable are inorganic acids such as hydrochloric acid,hydrobromic acid and sulfuric acid; and organic acids such asp-toluenesulfonic acid, methanesulfonic acid, acetic acid andtrifluoroacetic acid. A base to be used is also not particularlylimited. Suitable are inorganic salts such as sodium carbonate,potassium carbonate and sodium bicarbonate; alcoholates such as sodiummethoxide, sodium ethoxide and potassium tert-butoxide; metal amidessuch as sodium amide and lithium diisopropylamide. A solvent used isdifferent depending upon a raw material, a reagent and the like to beused, and is not particularly limited as long as it does not inhibit thereaction and dissolves a starting material to some extent. Suitablesolvents are alcohols such as methanol ethanol, isopropyl alcohol andethylene glycol; ethers such as diethyl ether, tetrahydrofuran, dioxaneand 1,2-dimethoxyethane; hydrocarbons such as benzene and toluene;amides such as N,N-dimethylformamide; acetonitrile; water, or a mixedsolvent of them.

[0312] A compound (I-3) of the present invention can be obtained byreacting a carboxylic acid (18) at normal pressure or under pressure at−80 to 250° C. in the presence of absence of a condensing agent and inthe presence or absence of a base in a solvent or without a solvent. Thecondensing agent used is different depending upon a starting rawmaterial, a reagent, the solvent and the like, and is not particularlylimited. Suitable condensing agents are dicyclohexylcarbodiimide,N-ethyl-N′-(3-dimehylaminopropyl)carbodiimide, carbonyldiimidazole,2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, a combination oftriphenylphosphine and carbon tetrachloride, diethyl chlorophosphate andthe like. The base used is different depending upon a starting rawmaterial, a reagent, the solvent and the like, and is not particularlylimited. Suitable bases are amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine and pyridine; inorganicsalts such as sodium carbonate, potassium carbonate and sodiumbicarbonate; alcoholates such as sodium methoxide, sodium ethoxide andpotassium tert-butoxide; metal amides such as sodium amide and lithiumdiisopropylamide. A solvent used is different depending upon a rawmaterial, a reagent and the like to be used, and is not particularlylimited as long as it does not inhibit the reaction and dissolves astarting material to some extent. Suitable solvents are alcohols such asmethanol, ethanol, isopropyl alcohol and ethylene glycol; ethers such asdiethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane;hydrocarbons such as benzene, toluene and xylene; amides such asN,N-dimethylformamide; acetonitrile; water, or a mixed solvent of them.

[0313] Among compounds represented by the above formula (I) according tothe present invention, the compound (I-4) in which the partial structure-A-B-D- is represented by the formula —CH═C(R²)—N(R³″)— (wherein R³″represents hydrogen atom, the formula —COR¹⁰ (wherein R¹⁰ represents aC₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄ alkyl group, anoptionally substituted aryl group, an optionally substituted heteroarylC₁₋₄ alkyl group or an optionally substituted heteroaryl group), a grouprepresented by the formula —S(O)_(p)R¹¹ (wherein R¹¹ represents a C₁₋₆alkyl group, an optionally substituted aryl C₁₋₄ alkyl group or anoptionally substituted aryl group, an optionally substituted heteroarylC₁₋₄ alkyl group or an optionally substituted heteroaryl group; and pmeans an integer of 0, 1 or 2), a C₁₋₁₀ alkyl group optionallysubstituted with any one or more groups listed in the above A group, aC₂₋₁₀ alkyenyl group optionally substituted with any one or more groupslisted in the above A group, a C₂₋₁₀ alkynyl group optionallysubstituted with any one or more groups listed in the above A group, ora C₃₋₈ cycloalkyl group optionally fused with an optionally substitutedbenzene ring and optionally substituted with a C₁₋₄ alkyl group) can beprepared by the following method:

[0314] wherein R², R³″, R⁷, M and W have the same meanings as definedabove.

[0315] The present reaction is usually performed in the presence of abase or in the presence of an oxidizing agent and in the solvent orwithout a solvent. A base used is different depending upon a startingraw material, a reagent, the solvent used and the like, and is notparticularly limited. Suitable bases are amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine and pyridine; inorganicsalts such as sodium hydroxide, potassium hydroxide, sodium carbonate,potassium carbonate and sodium bicarbonate; alcoholates such as sodiummethoxide, sodium ethoxide and potassium tert-butoxide; metal amidessuch as sodium amide, lithium diisopropylamide and lithiumbis(trimethylsilyl)amide; metal hydrides such as sodium hydride,potassium hydride and calcium hydride; organic magnesium compounds suchas methylmagnesium bromide and ethylmagnesium bromide; organic lithiumcompounds such as butyllithium and methyllithium. As an oxidizing agentused, for example, a metal reagent such as activated maganese dioxide;and organic compounds such as DDQ are preferable. A solvent used isdifferent depending upon a raw material, a reagent and the like to beused, and is not particularly limited as long as it does not inhibit thereaction and dissolves a starting material to some extent. Suitablesolvents are alcohols such as methanol ethanol, isopropyl alcohol andethylene glycol; ethers such as diethyl ether, tetrahydrofuran, dioxane,1,2-dimethoxyethane and diphenyl ether; hydrocarbons such as benzene,toluene and xylene and the like; halogenated hydrocarbons such asdichloromethane and chloroform; amides such as N,N-dimethylformamide and1-methyl-2-pyrrolidinone; alkylnitriles such as acetonitrile; ketonssuch as acetone and methyl ethyl keton; water, or a mixed solventthereof. A reaction temperature is different depending upon a lawmaterial, a reagent, the solvent and the like to be used, and is usually−80 to 300° C.

[0316] A compound wherein the partial structure -A-B- is represented bythe formula —CH₂—CH(R²)—CH₂—; and D is a substituted nitrogen atom in acompound represented by the above formula (I) of the present inventioncan be prepared by the following method:

[0317] wherein R², R³′, R^(a), R^(b), E, G, W, M¹ and X have the samemeanings as defined above; and K′ represents nitrogen atom or NH.

[0318] An intermediate compound (22) can be obtained by heatingcompounds (20) and (21) in the presence of an acid or Lewis acid in asolvent not involved in the reaction (Step 5-A). The present reaction isusually performed by heating in the presence of p-toluenesulfonic acid,sulfuric acid or hydrogen chloride in benzene, toluene or xylene, orheating in the presence of stannic chloride, zinc chloride/hydrogenchloride or aluminium chloride in a solvent such as dichloroethane,chloroform or diphenyl ether, or heating in a polyphosphoric acid.

[0319] A formyl compound (23) can be obtained by reducing a carboxylicacid compound (22) (Step 5-B). A reducing agent used is differentdepending upon a starting raw material, reagent, the solvent and thelike, and is not particularly limited. Suitable reducing agents arediisobutylaluminum hydride, lithium borohydride and the like. A solventused is different depending upon a raw material, a reagent and the liketo be used, and is not particularly limited as long as it does notinhibit the reaction and dissolves a starting material to some extent.Suitable solvents are tetrahydrofuran, dichloromethane and the like. Areaction temperature is usually −78° C. to the boiling point of thesolvent, preferably −78 to 20° C.

[0320] A compound (25) can be obtained by subjecting a compound (23)together with a compound (24) to Horner-Emmons reaction or Wittig-Hornerreaction in the presence of a base (Step 5-C). A base used is differentdepending upon a starting raw material, a reagent, the solvent and thelike, and is not particularly limited. Suitable bases are sodiumhydride, sodium alkoxide, n-butyllithum, potassium t-butoxide, lithiumbistrimethylsilylamide and the like. A solvent used is differentdepending upon a raw material, a reagent and the like to be used, and isnot particularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable solvents areN,N-dimethylformamide, n-hexane, tetrahydrofuran, diethyl ether and thelike. A reaction temperature is usually −78° C. to the boiling point ofthe solvent, preferably −78 to 20° C.

[0321] A compound (26) can be obtained by reducing a double bond of anene compound (25) (Step 5-D). As the reducing method used, for example,there is a hydrogenation using a metal catalyst such as Pd—C, Raneynickel and the like. A reaction solvent used is different depending upona raw material, a reagent and the like to be used, and is notparticularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable solvents areethanol, ethanol, tetrahydrofuran and the like. A reaction temperatureis usually −78° C. to the boiling point of the solvent, preferably 0 to20° C.

[0322] An alcohol compound (27) can be obtained by reducing a carboxylicacid of a compound (26) (Step 5-E). Preferable examples of the reducingagent used are diisobutylaluminium hydride, lithium borohydride and thelike. A reaction solvent used is different depending upon a rawmaterial, a reagent and the like to be used, and is not particularlylimited as long as it does not inhibit the reaction and dissolves astarting material to some extent. Preferred are tetrahydrofuran,dichloromethane and the like. A reaction temperature is usually −78° C.to the boiling point of the solvent, preferably −78 to 20° C.

[0323] Dihalogeno compound (28) can be obtained by reacting a compound(27) and a halogenating agent in the presence or absence of a base andthe presence or absence of a quaternary salt (Step 5-F). As thehalogenating agent and the reaction solvent used, and a reactiontemperature, those similar to the reagent, solvent and temperaturedescribed in Step 1-D in the above preparation method 1 can be used,respectively.

[0324] A compound (I-5) of the present invention can be obtained byreacting a dihalogeno compound (28) and a primary amine (10) at −80 to250° C. in the presence or absence of a base and in the presence orabsence of a solvent (Step 5-G). The present reaction can be performedaccording to the same as or similar to the condition for the above Steps1-E, 1′-C and 1′-D.

[0325] A compound wherein A is a group represented by the formula—CH₂—CH(R²)—, B is a group represented by the formula —CO— and D is agroup represented by the formula —N(R³′)— in a compound represented bythe above formula (I) of the present invention can be prepared by amethod represented by the formula:

[0326] wherein R², R³′, R^(c), E, G, W, M¹, X and K′ have the samemeanings as defined above.

[0327] That is, first, a compound (26) obtained in Step 5-D in the abovePreparation method 5 is halogenated with a halogenating agent, toprepare a compound (29). The (29) is treated with a primary amine (10),to give an aminoester compound (30) (Step 6-A; the same reactionconditions as those described in the above Step 5-F). Next, an esterpart of the compound (30) is hydrolyzed, to prepare an animocarboxylicacid compound (31) (Step 6-B; the same procedures as those described inthe above Step 3-D) and, finally, the compound (31) is treated accordingto the procedures described in the above Step 3-E, to give a δ lactamcompound (I-6) of the present invention.

[0328] When a compound (32) having as a substituent at 3-position a ringAr having a leaving group (a group represented by the symbol -Lev in thefollowing formula) is used as a raw material, a compound (I-7) of thepresent invention can be prepared by converting a leaving group -Lev ona ring Ar into a desired substituent R^(d) in accordance with a methodrepresented by the formula:

[0329] wherein M¹, R¹, R², R³ and R⁷ have the same meanings as definedabove; the ring Ar represents an aromatic group such as phenyl group,naphthyl group and heteroaryl group; Lev represents a leaving group suchas a halogen atom and trifluoromethanesulfonyl group; R^(d) and R^(d)′are the same as or different from each other and each representshydrogen atom, hydroxyl, nitro group, cyano group, carboxyl group, aC₁₋₆ alkyloxycarbonyl group, formula —S(O)_(p)R¹² (wherein R¹²represents hydrogen, a C₁₋₆ alkyl group, an optionally substituted arylC₁₋₄ alkyl group, an optionally substituted aryl group, an optionallysubstituted heteroaryl C₁₋₄ alkyl group or an optionally substitutedheteroaryl group; and p means an integer of 0, 1 or 2), —NR¹³R¹⁴(wherein R¹³ and R¹⁴ are the same as or different from each other andeach represents hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₄ alkylacylgroup), a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a C₃₋₈ cycloalkyl groupoptionally substituted with a C₁₋₄ alkyl group, a C₁₋₄ alkoxy C₁₋₆ alkylgroup, a C₂₋₁₀ alkenyl group, a saturated 3- to 8-membered heterocyclicring optionally substituted with a C₂₋₁₀ alkynyl group, an optionallysubstituted aryl group or an optionally substituted heteroaryl group;R^(d) represents an alkyl group, cyano group, an optionally substitutedaryl group, an optionally substituted alkynyl group, an alkoxycarbonylgroup, N-monosubstituted carbamoyl group and the like.

[0330] That is, 1) a compound represented by the formula (32) is heatingtogether with cuprous cyanide, zinc cyanide or the like in a highboiling point solvent such as N-pyrrolidinone, dimethylsulfoxide andN,N-dimethylformamide. Then, 2) it is subjected to anoxidative-reductive leaving reaction using a palladium catalyst to aleaving group Lev into R^(d). In such the conversion reaction, apalladium catalyst used is different depending upon a starting rawmaterial and the like, and is not particularly limited. Preferred arePd(PPh₃), Pd₂(dba)₃+L, Pd(OCOCH₃)₂+L, PdCl₂L₂ and the like (wherein Lmeans PPh₃, ddpe, dppf and the like). The reaction is usually performedat room temperature or under heating in the presence of a tertiary aminein a solvent. The tertiary amine used is different depending upon astarting raw material, a reagent, a solvent and the like, and is notparticularly limited. Preferably, triethylamine, diisopropylethylamine,DBU, dimethylaniline and the like may be proposed. A solvent used isdifferent depending upon a raw material, a reagent and the like, and isnot particularly limited as long as it dose not inhibit the reaction anddissolves a starting material to some extent. Preferably, ethers such astetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol,dimethylformamide, 1-methylpyrrolidine and the like may be proposed. Asuitable reaction temperature is 0 to 250° C. More suitable is underreflux.

[0331] In the compound according to the present invention represented bythe above formula (I), a compound wherein the partial structure -A-B-D-is represented by the formula —N═N—N(R³′)— is obtained by the methodshown by the formula:

[0332] wherein R³′, R^(a), E, G, W, M¹, X and K′ have the same meaningsas defined above; and R^(e)X represents an alkyl halide, a sanchloride,acid anhydride and the like.

[0333] First, a halogenated compound (33) which is a starting materialis obtained by halogenating a compound (22) obtained by the above Step5-B with a halogenating agent. The (33) is treated with (10), to give anaminoester compound (34) (Step 8-A). Such the step can be performedunder the same conditions as those for the above Step 5-F.

[0334] A hydrazide compound (35) is obtained by heating a compound (34)with hydrazine in a solvent (Step 8-B). Such the hydrazine is preferablyused at an excessive amount in an equivalent relationship relative to acompound (34). A reaction solvent used is different depending upon a rawmaterial used, a reagent used and the like and is not particularlylimited as long as it dose not dissolves a starting material to someextent. Suitable are alcohols such as methanol, ethanol, propanol,isopropanol and butanol, tetrahydrofuran, N-pyrrolidone,dimethylsulfoxide, N,N-dimethylformamide and the like.

[0335] An imidazolone compound (36) is obtained by acting sodium nitriteto a compound (35) (Step 8-C). The present reaction is performed byapplying the conditions for Curtius rearrangement reaction. A reactionsolvent used is different depending upon a raw material, a reagent andthe like to be used, and is not particularly limited as long as it dosenot inhibit the reaction and dissolves a starting material to someextent. Suitable are alcohols such as methanol, ethanol, propanol,isopropanol and butanol, tetrahydrofuran, N-pyrrolidinone,dimethylsulfoxide, N,N-dimethylformamide and the like.

[0336] Pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine compound can be preparedby two methods using an imidazolone compound (36) as a raw material.

[0337] That is, first, the first method is a method of reacting acompound (36) with an alkylating agent containing a leaving group suchas alkyl halide, or an acylating agent such as acid chloride, acidanhydride and the like at −70 to 200° C., to give the compound (I-8a)according to the present invention. A solvent used is differentdepending upon a raw material used, a reagent and the like to be used,and is not particularly limited as long as it dose not inhibit thereaction and dissolves a starting material to some extent. Suitable aretetrahydrofuran, diethyl ether, N,N-dimethylformamide, dimethylsulfoxideand the like. In addition, a base used is different depending upon a rawmaterial, a reagent, a solvent and the like to be used, and is notparticularly limited. Suitable are sodium hydride, potassium hydride,potassium carbonate, sodium carbonate, cesium carbonate, potassiumhydroxide, sodium hydroxide and the like.

[0338] The second method is a method of preparing a compound (38) byhalogenating a compound (36) (Step 8-E), then subjecting the (38) to ahydrogenation reaction, to give an imidazole derivative (I-8b) accordingto the present invention (Step 8-F). Step 8-E is performed in thepresence or absence of a base, and in the presence or absence of aquaternary salt. A base, a quaternary salt and a halogenating agent tobe used are different depending upon a starting raw material, a reagent,a solvent and the like, and are not particularly limited. Suitable basesare N,N-dimethylaniline, N,N-diethylaniline, N,N-diisopropylethylamineand the like. Suitable quaternary amines are tetraethylammonium bromide,tetraethylammonium chloride, triethylmethylammonium bromide,triethylmethylammonium chloride and the like. In addition, suitablehalogenating agents are thionyl chloride, phosphorus oxychloride,phosphorus trichloride, phosphorus pentachloride, phosphorousoxybromide, phosphorous tribromide, phosphorous pentabromide, oxazolylchloride and the like. A reaction temperature is usually −20 to 150° C.A hydrogenation reaction in Step 8-F is usually performed in a solventor without a solvent, in the presence or absence of an acid, and in thehydrogen atmosphere. A pressure of hydrogen is preferably 1 to 100 atm.Suitable examples of solvent used are methanol, ethanol, propanol,butanol, tetrahydrofuran, dioxane, ethyl acetate, acetone,N,N-dimethylformamide and the like. An acid used preferably is aceticacid, hydrochloric acid and the like. In addition, the hydrogenationreaction usually uses a metal catalyst and suitable examples thereof arePd—C, PtO₂, Pt—C, Raney-Ni and the like. A reaction temperature isusually 0 to 200° C. In addition, as a method according to this method,the compound according to the present invention may be prepared bygenerating hydrogen in situ by heating ammonium formate and the like ina solvent.

[0339] By using as a starting material the compound (I-2) of the presentinvention obtained in the above Preparation method 2, a compound of thepresent invention can be prepared newly by the following Preparationmethod 9.

[0340] wherein R¹, R², R³′, R⁷, X, W and s have the same meanings asdefined above; M² represents cyano group, or a group represented by theformula —NR¹³R¹⁴ (wherein R¹³ and R¹⁴ have the same meanings as definedabove), —OR¹⁵ (wherein R¹⁵ has the same meaning as defined above), —SHor —SR¹⁶ (wherein R¹⁶ has the same meaning as defined above); M³represents cyano group, or a group represented by the formula —NR¹³R¹⁴(wherein R¹³ and R¹⁴ have the same meanings as defined above), —OR¹⁵(wherein R¹⁵ has the same meaning as defined above), —SH or —S(O)_(q)R¹⁶(wherein q and R¹⁶ have the same meanings as defined above); Zrepresents hydrogen atom or an alkali metal (for example, sodium,potassium and the like); R^(f) represents (i) hydrogen atom, (ii) a C₃₋₈cycloalkyl group optionally fused with an optionally substituted benzenering, and optionally substituted with a C₁₋₄ alkyl group or (iii) a C₁₋₄alkyl group optionally substituted with any one or more groups listed inthe above A group; and R^(g) represents (i) a C₃₋₈ cycloalkylethyl groupoptionally fused with an optionally substituted benzene ring, andoptionally substituted with a C₁₋₄ alkyl group or (ii) a C₂₋₆ alkylgroup optionally substituted with any one or more groups listed in theabove A group.

[0341] 1) As the first method, there is a method of treating a compound(I-2) with a nuclephole represented by the formula M²-Z, to give acompound represented by the formula (I-9a) according to the presentinvention (Step 9-A). The present reaction can be performed by thesimilar reaction conditions to those for the above Step 5-F. Inaddition, a sulfinyl compound and a sulfonyl compound can be obtained byoxidizing a thiol compound or a sulfide compound obtained by the presentpreparation method by the conventional method known to a person skilledin the art.

[0342] 2) The second method is a method of reacting a compound (I-2)with an alkynyl compound represented by the formula R^(f)—C ≡CH, to givean ethynyl compound (I-9B) according to the present invention (Step9-B), or a method of reducing a compound (I-9b), to give a compound(I-9c) (Step 9-C). Step 9-B is usually performed at room temperature orunder heating in the presence of cuprous iodide and a tertiary amine. Areaction solvent used is different depending upon a raw material, areagent and the like to be used, and is not particularly limited as longas it dose not inhibit the reaction and dissolves a starting material tosome extent. Suitable are tetrahydrofuran, dioxane, dimethoxyethane,diethylene glycol dimethylether, N,N-dimethylformamide,1-methylpyrrolidinone and the like. Preferable examples in a tertiaryamine used are triethylamine, diisopropylethylamine, DBU,dimethylaniline and the like. A preferable reaction temperature is 0 to100° C., and a more preferable is room temperature. In addition, Step9-C can be performed by the conventional method by which a personskilled in the art can be easily performed.

[0343] The compound represented by the following formula (I-10)according to the present invention is obtained via Steps 10-A to D shownby the following formula:

[0344] wherein R^(b), E, G, K′, L, M¹, W, X and R^(e)X have the samemeanings as defined above.

[0345] In order to obtain a pyrazolone derivative (39) which is anintermediate, a compound (33) is reacted with hydrazine at 0 to 200° C.in the presence or absence of an acid in an inert solvent (Step 10-A).An acid used is different depending upon a starting raw material,reagents, the solvent and the like, and is not particularly limited.Suitable are inorganic acids such as hydrochloric acid, hydrobromic acidand sulfuric acid; organic acids such as p-toluenesulfonic acid,methanesufonic acid, acetic acid and trifluoroacetic acid. An inertsolvent used is different depending upon a raw material, reagents andthe like to be used, and is not particularly limited as long as it dosenot inhibit the reaction and dissolves a starting material to someextent. Suitable are alcohols such as methanol, ethanol, isopropanol andethylene glycol; ethers such as diethyl ether, tetrahydrofuran, dioxaneand 1,2-dimethoxyethane; hydrocarbons such as benzene, toluene andxylene; amides such as N,N-dimethylformamide; acetonitrile; water, or amixed solvent thereof.

[0346] In order to prepare (40) from a compound (39), the compound (39)is reacted with an alkylating agent containing a leaving group (forexample, alkyl halide and the like) or an acylating agent and the like(for example, acid chloride, acid anhydride and the like) at −70 to 200°C. in the presence or absence of a base in a solvent or without asolvent (Step 10-B). A solvent used is different depending upon a rawmaterial, reagents and the like to be used, and is not particularlylimited as long as it dose not inhibit the reaction and dissolves astarting material to some extent. Suitable are tetrahydrofuran, diethylether, dimethylformamide, dimethyl sulfoxide and the like. In addition,a base used is different depending upon a starting raw material,reagents, the solvent and the like, and is not particularly limited.Suitable are sodium hydride, potasssium hydride, potasssium carbonate,sodium carbonate, cesium carbonate, potasssium hydroxide, sodiumhydroxide and the like.

[0347] In addition, (40) can be prepared directly from a compound (33)instead of Steps 10-A and B (Step 10-A′). In such the reaction,hydrazine having a substituent on the nitrogen atom is used instead ofhydrazine used in Step 10-A.

[0348] Next, in Step 10-C, a pyrazolone compound (40) is reacted with ahalogenating agent at −20 to 150° C. in the presence or absence of abase and in the presence or absence of a quaternary salt, to give anintermediate (41) or (42). A base, a quaternary salt and a halogenatingagent to be used are different depending upon a starting raw material,reagents, the solvent and the like, and are not particularly limited.Suitable bases are dimethylaniline, diethylaniline,N,N-diisopropylethylamine and the like. Suitable quaternary salts aretetraethylammonium bromide, tetraethylammonium chloride,triethylmethylammonium bromide, triethylmethylammonium chloride and thelike. Suitable halogenating agents are thionyl chloride, phosphorusoxychloride, phosphorus trichloride, phosphorus pentachloride,phosphorous oxybromide, phosphorous tribromide, phosphorus pentabromide,oxalyl chloride and the like.

[0349] Finally, a compound (41) or a compound (42) is subjected to ahydrogenation reaction, to give a compound (I-10a or 10b) of the presentinvention (Step 10-D or D′). Such the reaction is conducted in thepresence or absence of an acid in a solvent or without a solvent inhydrogen atmosphere. A hydrogen pressure is preferably 1 to 100 atm.Suitable examples of the solvent used are methanol, ethanol, propanol,butanol, tetrahydrofuran, dioxane, ethyl acetate, acetone,N,N-dimethylformamide and the like. An acid used is preferably aceticacid, hydrochloric acid and the like. In addition, the hydrogenationreaction usually uses a metal catalyst, and suitable examples of themetal catalyst are Pd—C, PtO₂, Pt—C, Raney-Ni and the like. A reactiontemperature is usually 0 to 200° C. In addition, as an alternativemethod for the present method, the present compound may be prepared alsoby generating hydrogen in situ by heating ammonium formate and the likein a solvent.

[0350] In compounds of the present invention, a compound wherein A and Dare a group represented by the formula —CO— and B is represented by theformula —N(R^(3′)) can be prepared by a method represented by thefollowing formula:

[0351] wherein R^(3′), R^(b), E, E, G, K′, M¹, W and X have the samemeanings as defined above.

[0352] The first intermediate (43) is obtained by reacting a compound(33) with zinc cyanide at 0 to 200° C. in the presence of a 0 valentpalladium catalyst in N,N-dimethylformamide (Step-A).

[0353] Next, a compound (43) is hydrolyzed to prepare a compound (44)(Step 11-B) and, finally, such the (44) is reacted with an aminecompound (10), to give a phthalimide compound (I-11) of the presentinvention (Step 11-C). The above Step 11-B is performed in the presenceof an acid or a base, and in an inert solvent. An acid or a base used isdifferent depending upon a starting raw material, reagents, the solventand the like, and is not particularly limited. Suitable acids areinorganic acids such as hydrochloric acid, hydrobromic acid, sulfuricacid and the like, and suitable bases are inorganic salts such aspotassium hydroxide, sodium hydroxide, lithium hydroxide, sodiumcarbonate, potassium carbonate, sodium bicarbonate and the like;alcoholates such as sodium methoxide, sodium ethoxide, potassiumtert-butoxide, and the like. An inert solvent used is differentdepending upon a raw material, reagents and the like to be used and isnot particularly limited as long as it dose not inhibit the reaction anddissolves a starting material to some extent. Suitable are alcohols suchas methanol, ethanol, isopropyl alcohol and ethylene glycol; ethers suchas diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane;hydrocarbons such as benzene, toluene and xylene; amides such asN,N-dimethylformamide; acetonitrile, water or a mixed solvent thereof. Areaction temperature is usually 0 to 200° C. The above Step-C is usuallyperformed in a solvent such as acetic acid and the like. A reactiontemperature is usually 0 to 200° C.

[0354] In compounds represented by the formula (I) according to thepresent invention, a compound wherein D is oxygen atom is obtained bythe following preparation method:

[0355] wherein R², E, G, K′, M¹ and W have the same meanings as definedabove.

[0356] The present reaction is performed by reacting a dihydroxycompound (45) with thionyl chloride and the like in an inert solvent.After the reaction, the reaction system is cooled to room temperature,the precipitated crystals are collected by filtration, and the resultingcrystals are reacted with a base, to give finally a dihydrofurancompound (I-11) of the present invention. Preferable examples in thesolvent used are ethers such as diethyl ether, tetrahydrofuran, dioxaneand 1,2-dimethoxyethane; hydrocarbons such as benzene and toluene;acetonitrile, or a mixed solvent thereof. Preferable examples in a baseused are inorganic salts such as sodium carbonate, potassium carbonateand sodium bicarbonate; alcoholates such as sodium methoxide, sodiumethoxide and potassium tert-butoxide. A reaction temperature is usually0 to 200° C.

[0357] Further, compounds represented by the above formula (I) of thepresent invention, a compound wherein D is sulfur is obtained by thefollowing preparation method:

[0358] wherein R², E, G, K′, M¹ and W have the same meanings as definedabove.

[0359] The present reaction is usually performed in the presence of abase in an inert solvent. A base used is different depending upon astarting raw material, reagents, the solvent and the like, and is notparticularly limited. Suitable are amines such as triethylamine,diisopropylamine, N,N-diisopropylethylamine and pyridine; inorganicsalts such as soidum carbonate, potassium carbonate and sodiumbicarbonate; alcoholates such as sodium methoxide, sodium ethoxide andpotassium tert-butoxide; and the like. In addition, an inert solventused is different depending upon a raw material, reagents and the liketo be used, and is not particularly limited as long as it dose notinhibit the reaction and dissolves a starting material to some extent.Suitable are alcohols such as methanol, ethanol, isopropyl alcohol andethylene glycol; ethers such as diethyl ether, tetrahydrofuran, dioxaneand 1,2-dimethoxyethane; amides such as N,N-dimethylformamide;acetonitrile; water, or a mixed solvent thereof. A reaction temperatureis usually 0 to 200° C.

[0360] A compound wherein the partial structure -A-B-D- is an optionallysubstituted alkylene group in the above formula (I) can be prepared, forexample, by a method represented by the formula:

[0361] wherein R¹, R², E, G, K′, M¹ and W have the same meanings asdefined above.

[0362] A reaction is usually performed in an inert solvent and such theinert solvent is different depending upon a raw material, reagents andthe like to be used, and is not particularly limited as long as it doesnot inhibit the reaction and dissolves a starting material to someextent. Suitable are alcohols such as methanol, ethanol, isopropylalcohol and ethylene glycol; ethers such as diethyl ether,tetrahydrofuran, dioxane and 1,2-dimethoxyethane; hydrocarbons such asbenzene and toluene; amides such as N,N-dimethylformamide; acetonitrile;water, or a mixed solvent thereof, and the like. A reaction temperatureis usually 0 to 200° C.

[0363] Synthesis of a skeleton of a compound of the present inventioncan be conducted by the following method in addition to methodsdescribed in the above preparation methods.

[0364] wherein E, G, K′, M¹ and W have the same meanings as definedabove.

[0365] The present preparation method is a method of cyclization whilereducing a nitro group of a compound (48), and is performed in thepresence of a metal powder such as zinc powder and the like and an acidin an inert solvent or without a solvent. An acid used is differentdepending upon a starting material, reagents, the solvent and the like,and is not particularly limited. Suitable are inorganic acids such ashydrochloric acid, hydrobromic acid and sulfuric acid; and organic acidssuch as p-toluenesulfonic acid, methanesulfonic acid, acetic acid andtrifluoroacetic acid. An inert solvent used is different depending upona raw material, reagents and the like to be used, and is notparticularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable are alcohols suchas methanol, ethanol, isopropyl alcohol and ethylene glycol; ethers suchas diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxy ethane;hydrocarbons such as benzene and toluene; amides such asN,N-dimethylformamide; acetonitrile; water, or a mixed solvent thereofand the like. A reaction temperature is usually 0 to 200° C.

[0366] Alternatively, a hydrogenation reaction may be used in order toprepare an end compound (I-15) from a starting material in the presentpreparation method. Such the hydrogenation reaction is performed in thepresence or absence of an acid in the hydrogen atmosphere. A hydrogenpressure is preferably 1 to 100 atom. An acid and a solvent to be usedare different depending upon a starting material, reagents, the solventand the like, and are not particularly limited. Suitable acids areacetic acid, hydrochloric acid and the like, and suitable solvents aremethanol, ethanol, propanol, butanol, tetrahydrofuran, dioxane, ethylacetate, acetone, N,N-dimethylformamide and the like. In thehydrogenation reaction, a metal catalyst is usually used, and suitableexamples of such the metal catalysts are Pd—C, PtO₂, Pt—C, Raney-Ni andthe like. A reaction temperature is usually 0 to 200° C. In addition, asan alternative method for the present method, a compound of the presentinvention may be prepared also by generating in situ by heating ammoniumformate and the like in a solvent.

[0367] According to Preparation method 15, for example, an imidazolering can be introduced in a skeleton by a method shown in the formula:

[0368] In a compound represented by the above formula (I) according tothe present invention, a compound containing a pyrazole ring on theskeleton and compound having a substituent on the nitrogen atom on theskeleton ring can be prepared by the following method:

[0369] wherein R², R³′, R⁷, M¹ and s have the same meanings as definedabove; and Ar represents an aromatic group having a substituent.

[0370] A pyrazole ring compound (51) as a starting material can beprepared according to the method described in WO99/10350 (Step 16-A).

[0371] A compound (53) is obtained by dehydration condensation of the(51) and α-ketoester (52) (Step 16-D). A solvent used is differentdepending upon a raw material, reagents and the like, and is notparticularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable are xylene,toluene, benzene, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, ethanoland the like. In addition, the present reaction can afford the betterresults by adding a dehydration agent, and preferable examples in suchthe dehydration agent are acids such as hydrochloric acid, sulfuricacid, p-toluenesulfonic acid, acetic acid, trifluoacetic acid, oxalicacid and phosphoric acid. A reaction temperature is usually roomtemperature to the boiling point of the solvent, preferably the boilingpoint of the solvent.

[0372] Next, a compound (54) is obtained by halogenating a compound (53)(Step 16-C) A halogenating agent used is different depending upon astarting material, reagents, a solvent and the like, and is notparticularly limited. Suitable are phosphorus oxychloride, phosphorusoxybromide and the like. Halogenation is performed in a solvent orwithout a solvent, and such the solvent is different depending upon araw material, reagents and the like to be used, and is not particularlylimited as long as it does not inhibit the reaction and dissolves astarting material to some extent. Suitable are acetonitrile and thelike. Further, the present reaction is performed by adding a base andpreferable examples in such the base are triethylamine,diethylisopropylamine, pyridine, N,N-dimethylaminopyridine,N,N-dimethylaniline, N,N-diethylaniline and the like. A reactiontemperature is usually 0 to 120° C.

[0373] Further, in Step 16-D, a cyclizing reaction of a compound (54)and an amine compound (55) can be performed, to give a compound (56)(Step 16-D). A solvent used is different depending upon a raw material,reagents and the like to be used, and is not particularly limited aslong as it does not inhibit the reaction and dissolves a startingmaterial to some extent. Suitable are xylene, toluene, benzene,tetrahydrofuran, N-methylpyrrolidone, N,N-dimethylformamide,1,4-dioxane, dimethoxyethane, ethanol, acetonitrile and the like.Alternatively, an amine compound (55) may be used as a solvent. Thepresent reaction is preferably performed by adding p-toluenesulfonicacid, phenol and the like. A reaction temperature is usually roomtemperature to the boiling point of the solvent. However, when apressure-resistant vessel is used, a reaction may be performed in arange of the boiling point of the solvent to 200° C.

[0374] Finally, a compound (I-16) of the present invention is obtainedby subjecting a compound (56) to an oxidation reaction (Step 16-G). As apreferable example in such the oxidation reaction, there are oxidationwith manganese dioxide, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ),air oxidation and the like.

[0375] In the formula, R¹, R², R³′, E, G, K′, M¹, W, X and s have thesame meanings as defined above. A dihydropyrrole compound (58) can beprepared by a method according to the above Preparation method 1 and thelike (Step 17-A). A compound (I-17) of the present invention can beobtained by reacting the compound (58) with a heteroaryl-boric acidcompound, an aryl-boric acid compound, an aryl-metal compound or acompound (59) (for example, a heteroaryl-tin compound, an aryl-tincompound and the like) (Step 17-B). The reaction is performed by using apalladium or nickel metal complex. Preferable examples thereof arePd(PPh₃)₄, Pd(OAc)₂/PPh₃, PdCl₂, PdCl₂ (dppf), Ni(dpp)₂Cl₂ and the like.A solvent used is different depending upon a raw material, reagents andthe like to be used and is not particularly limited as long as it doesnot inhibit the reaction and dissolves a starting material to someextent. Suitable are benzene, toluene, xylene, anisole,N,N-dimethylformamide, 1,2-dimethoxyethane, tetrahydrofuran, dioxane,n-butanol, ethanol, methanol, N-methyl-2-pyridone or water, or a mixedsolvent thereof. A reaction temperature is usually 0 to 250° C. Inaddition, the present reaction is a reaction which is performed in thepresence of a base, such the base is different depending upon a startingmaterial, reagents, the solvent and the like, and is not particularlylimited. Suitable are potassium carbonate, sodium carbonate, cesiumflouride, potassium fluoride, sodium bicarbonate, triethylamine and thelike.

[0376] As the alternative method for the above preparation methods 15and 15′, there is a method of adding iodine to a position of W in theformula (Preparation method 18).

[0377] wherein R¹, R², R³, E, G, K′ and M¹ have the same meanings asdefined above; and NIS means N-Iodosuccinimide.

[0378] That is, a prepared iodo compound (64) is converted into anacatylene derivative (66), and from the (66), an aniline derivative (67)is synthesized, to finally prepare a benzimidazole derivative (I-18) ofthe present invention.

[0379] First, a compound (66) is obtained by reacting an iodo compound(64) with a protected trimethylsilylacetylene (65) in the presence of apalladium catalyst and a base in an inert solvent in the system where asuitable catalyst is further added, then treating with a deprotectingreagent (Step 18-A). Such the ‘suitable catalyst’, a base and adeprotecting reagent to be used are different depending upon a startingmaterial, reagents, the solvent and the like, and are not particularlylimited. Preferable examples in ‘suitable catalyst’ are cuprous iodideand the like. Suitable bases are potassium carbonate, sodium carbonate,cesium fluoride, potassium fluoride, sodium bicarbonate, triethylamineand the like. In addition, suitable deprotecting reagents are fluorineanion and the like, more preferably tetrabutylammonium fluoride, cesiumfluoride and the like. Suitable examples in a palladium catalyst or anickel metal complex used are Pd(PPh₃)₄, Pd(OAc)₂/PPh₃, PdCl₂,PdCl₂(dppf), Ni(dpp)₂Cl₂ and the like. A solvent used is differentdepending upon a raw material, reagents and the like to be used, and isnot particularly limited as long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable are benzene,toluene, xylene, anisole, N,N-dimethylformamide, 1,2-dimethoxyethane,tetrahydrofuran, n-butanol, ethanol, methanol, N-methyl-2-pyridone,water, or a mixed solvent thereof and the like. A reaction temperatureis usually 0 to 250° C.

[0380] An aniline derivative (67) which is a next intermediate isobtained by reacting an acetylene compound (66) with 2-iodoaniline inthe presence of a palladium catalyst and a base in an inert solvent inthe system where a suitable catalyst is further added (Step 18-B).‘Suitable catalyst’ used is different depending upon a startingmaterial, reagents, the solvent and the like, and is not particularlylimited. Suitable examples of ‘suitable catalyst’ are cuprous iodide andthe like. Suitable bases are potassium carbonate, sodium carbonate,cesium fluoride, potassium fluoride, sodium bicarbonate, triethylamineand the like. In addition, suitable examples in a palladium or a nickelmetal complex used are Pd(PPh₃)₄, Pd(OAc)₂/PPh₃, PdCl₂, PdCl₂ (dppf),ni(dpp)₂Cl₂ and the like. A solvent used is different depending upon araw material, reagents and the like to be used, and is not particularlylimited as long as it does not inhibit the reaction and dissolves astarting material to some extent. Suitable are benzene, toluene, xylene,anisole, N,N-dimethylformamide, 1,2-dimethoxyethane, tetrahydrofuran,N-butanol, ethanol, methanol, N-methyl-2-pyridone, water, or a mixedsolvent thereof and the like. A reaction temperature is usually 0 to250° C.

[0381] Finally, in order to obtain a benzimidazole derivative (I-18) ofthe present invention form the above compound (67), an aniline compound(67) is reacted at 0 to 250° C. in the presence of a catalyst such ascuprous iode and the like in an inert solvent. A solvent used isdifferent depending upon a raw material, reagents and the like to beused, and is not particularly limited as long as it does not inhibit thereaction and dissolves a starting material to some extent. Suitable arebenzene, toluene, xylene, anisole, N.N-dimethylformamide,1,2-dimethoxyethane, tetrahydrofuran, dioxane, n-butanol, ethanol,methanol, N-methyl-2-pyridone, water, or a mixed solvent thereof and thelike.

[0382] In addition, there is a method of preparing a compound of thepresent invention via an aldehyde intermediate (Preparation method 19).

[0383] wherein R¹, R², R³, E, G, K′ and M¹ have the same meanings asdefined above; and R^(h) and R^(i) represent a substituent.

[0384] That is, first, a benzimidazole derivative (I-19) of the presentinvention is prepared by formylating a compound (63) by a method such asVilsmeier method (compound (68); Step 19-A), then reacting the aldehydecompound with 1,2-phenylenediamine derivative (69) (Step 19-B). Theabove formylating reaction (Step 19-A) is usually performed at areaction temperature of 0 to 100° C. When a Vilsmeier method is used inthe formylating reaction, phosphoryl chloride and N,N-dimethylformamideare reacted, to synthesize a Vilsmeier reagent, and such the reagent isused to perform a reaction. A reaction of an aldehyde compound (68) anda 1,2-phenylenediamine derivative (69) is performed at 0 to 250° C. inthe presence of a catalyst in an inert solvent (Step 19-B). A catalystused is different depending upon a starting raw material, reagents, thesolvent and the like, and is not particularly limited. Suitable are2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and the like. Inaddition, the solvent used is different depending upon a startingmaterial, reagents, the solvent and the like, and is not particularlylimited. Suitable are N,N-dimethylformamide, 1,2-dimethoxyethane,tetrahydrofuran, dioxane, n-butanol, ethanol, methanol,N-methyl-2-pyridone, water, or a mixed solvent thereof and the like.

[0385] A compound having a skeleton of a 6-6-5-membered ring system incompounds of the present invention can be prepared, for example, by thefollowing method (Preparation method 20).

[0386] wherein R², R^(3′), M¹, X and Ar have the same meanings asdefined above; R^(j), R^(k), R^(l) and R^(m) represent nitrogen atom ora group represented by the formula —C(R⁷)— (wherein R⁷ has the samemeaning as defined above); Q represents a group represented by theformula —B(R^(n))₂, —Sn(R^(o))₃ (wherein R^(n) and R^(o) are the same asor different from each other and each represents an alkyl group and thelike), —ZnX′ or —MgX″ (wherein X′ and X″ represent the same or differenthalogen atom); and t means an integer of 0, 1 or 2.

[0387] In order to prepare a compound (74), there are a method viacompounds (70) and (71) (Step 20-A, B), a method of deriving from acompound (72) (Step 20-C), and a method of deriving from a compound (73)(Step 20-D).

[0388] A compound (71) is obtained by a palladium catalystcross-coupling reaction of (70) and an organometal compound (20-A). Anorganometal compound used is different depending upon a startingmaterial, reagents, the solvent and the like, and is not particularlylimited. Suitable are an organic boron compound, an organic tincompound, an organic zinc compound, Grignard reagent and the like. Asolvent used is different depending upon a raw material, reagents andthe like to be used, and is not particularly limited as long as it doesnot inhibit the reaction and dissolves a starting material to someextent. Suitable are organic solvents such as toluene, benzene andtetrahydrofuran; hydrophilic organic solvents such asN,N-dimethylformamide, 1,4-dioxane, 1,2-dimethoxyethan, ethanol andacetonitrile; a mixed solvent of a hydrophilic organic solvent andwater, and the like. A catalyst used is different depending upon astarting material, reagents, the solvent and the like, and is notparticularly limited. Suitably, tetrakistriphenylphosphine palladium,dichlorobistriphenylphosphine palladium and the like are used alone, ora mixture of palladium acetate, bisdibenzylydene aceton palladium andthe like with a phosphine compound such as triphenylphosphine is used. Asuitable example of a reaction temperature is room temperature to aboiling point of the solvent. In addition, when an organic boroncompound is used as an organometal compound, this cross-couplingreaction is usually performed in the presence of a base. As a preferableexample in the base, there are triethylamine, sodium carbonate,potassium carbonate, cesium carbonate, potassium tert-butoxide, sodiumhydroxide, barium hydroxide, potassium acetate, potassium phosphate andthe like.

[0389] A compound (74) can be obtained by reduction of a nitro compound(71) (Step 20-B), by a palladium catalyst cross-coupling reaction of anorganometal compound (72) and halogenated allyl (Step 20-C), or apalladium catalyst cross-coupling reaction of a compound (73) and anorganometal compound. As a preferable reduction reaction in step 20-B,for example, there are a catalytic hydrogenation reaction and areduction reaction using a metal salt such as iron, zinc and tin. Acoupling reaction in Steps 20-C and D can be performed under the sameconditions as the reaction conditions in the above Step 20-A.

[0390] In order to prepare a compound (I-20) of the present inventionfrom a compound (74), one can pass successively through Steps 20-G, H, Kand N in the formula.

[0391] First, a compound (80) can be obtained by dehydrationcondensation of a compound (74) and α-ketoester (76) (Step 20-G). Asolvent used is different depending upon a raw material, reagents andthe like to be used, and is not particularly limited as long as it doesnot inhibit the reaction and dissolves a starting material to someextent. Suitable are xylene, toluene, benzene, tetrahydrofuran,1,4-dioxane, dimethoxyethane, ethanol and the like. The present reactioncan also afford the better results by adding an acid such ashydrochloric acid, sulfuric acid, p-toluenesulfonic acid, acetic acid,trifluoroacetic acid, oxalic acid, phosphoric acid and the like as adehydration agent. A reaction temperature is usually room temperature toa boiling point of the solvent, preferably a boiling point of thesolvent.

[0392] A compound (81) can be obtained by halogenating a compound (80)(Step 20-H) and, additionally, also can be obtained by a palladiumcatalyst cross-coupling reaction of a compound (77) derived from acompound (73) and an organometal compound (Step 20-I). A halogenatingagent and a solvent used in Step 20-H are different depending upon astarting material, reagents, a solvent and the like, and are notparticularly limited. Suitable halogenating agents are phosphorousoxychloride, phosphorous oxybromide and the like. Suitable solvents areacetonitrile and the like. In addition, such the halogenating reactioncan be also performed without a solvent. Further, the presenthalogenating reaction can afford more preferable results by adding abase such as triethylamine, diethylisopropylamine, pyridine,N,N-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline andthe like. A reaction temperature is usually 0 to 120° C., but thereaction may be also performed at 120 to 180° C., when anpressure-resistance vessel is used. A cross-coupling reaction in Step20-I can be performed under the same conditions as the reactionconditions for the above Step 20-A.

[0393] A compound (82) can be obtained by a cyclization using an amine(10) (Step 20-K). The present reaction is usually performed in thepresence of a solvent, and is also preferable by addingp-toluenesulfonic acid, phenol and the like. A solvent used is differentdepending upon a raw material, reagents and the like to be used, and isnot particularly limited so long as it does not inhibit the reaction anddissolves a starting material to some extent. Suitable examples arexylene, toluene, benzene, tetrahydrofuran, N-methylpyrrolidone,N,N-dimethylformamide, 1,4-dioxane, dimethoxyethane, ethanol,acetonitrile and the like. Alternatively, an amine (10) may be used as asolvent instead of them. A reaction temperature is usually roomtemperature to a boiling point of the solvent, and the reaction may bealso performed at a boiling point of the solvent to 200° C., when apressure-resistant vessel is used.

[0394] Finally, a compound (I-20) of the present invention can beobtained by oxidizing a compound (82) (Step 20-N). As a preferableexample in such the oxidation reaction, there are a manganese dioxideoxidation, a 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation,an air oxidation and the like.

[0395] In order to prepare a compound (I-20) of the present inventionfrom a compound (73), one may pass successively thorough Steps 20-E, F,J, L and M in the formula or one may pass successively through Steps20E, F, I, K and N.

[0396] First, a compound (75) is obtained by dehydration condensation ofa compound (73) and α-ketoester (76) (Step 20-E). Such the condensationreaction can be performed under the same conditions as the reactionconditions for the above Step 20-G.

[0397] A compound (77) is obtained byhalogenating a compound (75) (Step20-F). Such the halogenating reaction can be performed under the sameconditions as the reaction conditions for the above Step 20-H.

[0398] A compound (78) can be obtained by a cyclization using an amine(10) (Step 20-J). Such the reaction can be performed under the sameconditions as the reaction conditions for the above Step 20-K.

[0399] A compound (79) can be obtained by oxidizing a compound (78). Asa preferable example in such the oxidation reaction, there are amanganese dioxide oxidation, a 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ) oxidation, an air oxidation and the like.

[0400] Finally, the compound (I-20) according to the present inventioncan be obtained by a palladium catalyst cross-coupling reaction of acompound (79) and an organometal compound. Such the cross-couplingreaction can be performed under the same conditions as the reactionconditions for the above Step 20-A.

[0401] The foregoing are methods of preparing a compound (I) of thepresent invention, raw material compounds listed in the abovepreparation methods may form a salt or a hydrate, and the kind of suchthe salt and whether hydrate or an hydride are not particularly limitedas long as they do not inhibit the reaction. When a compound of thepresent invention is prepared as a free compound, it can be convertedinto the state of a salt according to the conventional method. Inaddition, a variety of isomers (for example, geometrical isomer, opticalisomer based on an asymmetrical carbon, stereoisomer, tautomer and thelike) regarding a compound (I) of the present invention can be purifiedand isolated using the conventional separating means (for example,recrystallization, diastereomer salt method, enzyme dissolution method,a variety of chromatographies and the like).

[0402] A compound represented by the above formula (I) of the presentinvention, a salt thereof or hydrates thereof can be formulated intopreparations by the conventional method. As a preferable dosage form,there are tablets, powders, fine granules, granules, coated tablets,capsules, syrups, troches, inhalants, suppositories, injections,ointments, ocular ointments, eye drops, nasal drops, ear drops,cataplasms, lotions and the like. For the formulation into preparations,excipient, binding agent, disintegrating agent, lubricant, colorant andflavoring agent which are generally used and, if needed, stabilizer,emulsifier, absorption promoter, surfactant, pH adjusting agent,preservative and anti-oxidant can be used. Generally, ingredients usedas a raw material for pharmaceutical preparations can be blended andformulated into preparations by the conventional method. As theseingredients, there are animal and vegetable oils such as soy bean oil,beef tallow and synthetic glycerin; hydrocarbons such as liquidparaffin, squalene and solid paraffin; ester oils such as octyldodecylmyristate and isopropyl myristate; higher alcohols such as cetostearylalcohol and behenyl alcohol; silicone resin; silicone oil; surfactantssuch as polyoxyethylene fatty ester, sorbitan fatty ester, glycerinfatty ester, polyoxyethylenesorbitan fatty ester, polyoxyethylenehydrogenated castor oil and polyoxyethylene polyoxypropylene blockcopolymer; water-solublepolymers such as hydroxyethyl cellulose,polyacrylic acid, carboxyvinil polymer, polyethylene glycol,polyvinylpyrrolidole and methyl celluose; lower alcohols such as ethanoland isopropanol; polyhydric alcohol such as glycerin, propylene glycol,dipropylene glycol and sorbitol; sugar such as grucose and sucrose;inorganic powders such as anhydrous silicic acid, aluminium magnesiumsilicate and alminium silicate; purified water, and the like.Specifically, there can be used, for example, lactose, cornstarch,sucrose, glucose, mannitol, sorbitol, crystalline celluose, silicondioxide and the like as an excipient; for example, polyvinyl alcohol,polyvinyl ether, methyl celluose, ethyl celluose, gum arabic, tragacant,gelatin, shellac, hydroxypropyl celluose, hydroxypropylmethyl celluose,polyvinylpyrrolidone, polypropylene glycol polyoxiethylene blockpolymer, meglumine, calcium citrate, dextrin, pectin and the like as abinding agent; for example, starch, agar, gelatin powder, crystallinecelluose, calcium carbonate, sodium bicarbonate, calcium citrate,dextrin, pectin, calcium carboxymethyl celluose and the like as adisintegrating agent; for example, magnesium stearate, talc,polyethylene glycol, silica, hydrogenated vegetable oil and the like asa lubricant; any ones which are permitted to add to medicaments as acolorant; cacao powder, 1-menthol, aromatic powder, mentha oil, Borneocamphor, powdered cinnamon bark and the like as flavoring agent; and anyones which are permitted to add to phermaceuticals such as ascorbic acidand α-tocopherol as an anti-oxidant.

[0403] (1) For example, for oral preparations, a compound of the presentinvention, a salt thereof or hydrates thereof and an excipient, ifneeded, a binding agent, disintegrating agent, lubricant, colorant,flavoring agent and the like are added, and thereafter, formulated intopowders, fine granules, granules, tablets, coated tablets, capsules andthe like by the conventional method. (2) In the case of tablets orgranules, coating such as sugar coating, gelatin coating, and others maybe of course performed conveniently. (3) In the case of syrups,injectable preparations, eye drops and the like, a pH adjusting agent,dissolving agent, isotonic and the like and, if needed, a solubilizer,stabilizer, buffer, suspending agent and anti-oxidant are added andformulated in preparations by the conventional method. In thepreparations, it may be freeze-dried, and an injectable can be admiredintravenously, subcutaneously or intramascularly. There are methylcellose, polysorbate 80, hydroxyethyl cellouse, gum arabic, tragacantpowder, sodium carboxymethyl cellouse, polyoxyethylenesorbitanmonolaurate and the like as a preferable example in a suspending agent;polyoxyethylene hydrogenated castor oil, polysorbate 80, nicotinicamide, polyoxyethylenesorbitan monolaurate and the like as a preferableexample of a solubilizer; sodium sulfite, sodium methasulfite, ether andthe like as a preferable example of a stabilizer; and methylparaoxybenzoate, ethyl paraoxybenzoate, sorbic acid, phenol, cresol,chlorocresol and the like as a preferable example of a preservative. (4)In addition, in the case of an external preparation, a method ofpreparing it is not particularly limited but it can be prepared by theconventional method. As a base raw material used, a variety of rawmaterials which are usually used for a drug, a quasi-drug or a cosmeticcan be used and, for example, there are raw materials such as animal andvegetable oils, mineral oils, ester oils, waxes, higher alcohols, fattyacids, silicone oils, surfactants, phospholipids, alcohols, polyhydricalcohols, water-soluble polymers, clay minerals, purified water. Ifneeded, a pH adjusting agent, anti-oxydant, chelating agent, antisepticand anti-mold agent, colorant and flavor and the like may be added.Further, if needed, an ingredient having the differentiation inducingactivity, ingredients such as a blood flow promoter, sterilizer,anti-inflammatory, cell activating agent, vitamins, aminoacid,humectant, corneum dissolving agent and the like may be incorporated. Adose of a drug of the present invention is different depending uponseverity of the symptom, age, sex, weight, dosage form, kind of salt,difference in sensitivity to a drug, particular kind of disease and thelike, and generally about 30 μg to 1000 mg, preferably 100 μg to 500 mg,more preferably 100 μg to 100 mg is administered orally per day in anadult, and about 1 to 3000 μg/kg, preferably 3 to 1000 μg/kg isadministered by injection once or in several times.

EXAMPLES

[0404] The following Reference Examples, Examples (pharmacologicallyacceptable salts, hydrates thereof and pharmaceuticals containing them)and Test Examples are only illustrative and compounds of the presentinvention are not limited by the following embodiments. A person skilledin the art can implement the present invention to maximum by way ofExamples and by modifying claims and such the modification is includedin the claims.

Reference Examples 1 4-Mesityl-3-methyl-1H-5-pyrazoleamine

[0405] In tetrahydrofuran (700 mL) was dissolved 2-mesitylacetonitrile(50 g, 314 mmol). Under ice-cooling, sodium hydride (31 g (60%), 785mmol) was slowly added thereto, followed by stirring at room temperaturefor one hour. Under ice-cooling, ethyl acetate (92 mL, 942 mmol) wasadded thereto, followed by stirring at room temperature overnight.Methanol (100 mL) was added to the reaction mixture, followed byevaporating. The residue was subjected to silica gel columnchromatography (20% methanol/ethyl acetate), to give a crude purifiedproduct of 2-mesityl-3-oxobutanenitrile. A mixture of the resulting2-mesityl-3-oxobutanenitrile, hydrazine dihydrobromide (300 g), water(200 ml) and ethanol (1000 mL) was heated under reflux for six days. Thereaction mixture was evaporated and neutralized with an aqueoussaturated sodium bicarbonate solution. The resulting crystals werecollected by filtration, washed well with water and air-dried at 50° C.,to give the title compound (65 g) as gray-white crystals.

[0406]¹H-NMR (400 MHz, CDCl₃) δ2.03 (s, 3H), 2.07 (s, 6H), 2.32 (s, 3H),6.95 (s, 2H).

Reference Example 2 6-(2-Hydroxyethyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0407] A mixture of 4-mesityl-3-methyl-1H-5-pyrazoleamine (20 g, 99.2mmol) obtained in Reference Example 1, 2-acetylbutyrolactone (10.5 mL,97.5 mmol) and xylene (150 mL) was heated under reflux for five hours.It was cooled to room temperature, and the resulting crystals werecollected by filtration, to give the title compound (22.7 g) as whitecrystals.

[0408]¹H-NMR (400MHz, CDCl₃) δ2.03 (s, 6H), 2.15 (s, 3H), 2.33 (s, 3H),2.34 (s, 3H), 2.40(br s, 1H), 2.86 (t, J=6.0 Hz, 2H), 3.85 (t, J=6.0 Hz,2H), 6.98 (s, 2H), 8.13 (s, 1H).

[0409] According to the procedures described in the above ReferenceExamples, the following compounds were synthesized.

Reference Example 33-[6-(Dimethylamino)-4-methyl-3-pyridyl]-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0410] Flesh Colored Crystals

[0411]¹H-NMR (400 MHz, DMSO-d₆) δ1.99 (s, 3H), 2.06 (s, 3H), 2, 27 (s,3H), 2.59 (t, J=6.8 Hz, 2H), 3.04 (s, 6H), 3.45 (dt, J=6.0 Hz, 2H), 4.58(t, J=6.0 Hz, 1H), 6.61 (s, 1H), 7.83 (s, 1H), 11.46 (s, 1H).

Reference Example 46-(2-Hydroxyethyl)2,5-dimethyl-3-(3-methyl-2-naphthyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0412] White Crystals

[0413]¹H-NMR (400 MHz, CDCl₃+DMSO-d₆) δ2.21 (s, 3H), 2.26 (s, 3H), 2.28(s, 3H), 2.82 (t, J=6.4 Hz, 2H), 3.78 (t, J=6.0 Hz, 2H), 4.71 (br s,1H), 7.38-7.48 (m, 2H), 7. 67 (s, 1H), 7.73 (s, 1H), 7.75-7.78 (m, 2H).

Reference Example 53-(4-Bromophenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0414] White Crystals

[0415]¹H-NMR (400 MHz, DMSO-d₆) δ2.24 (s, 3H), 2.32 (s, 3H), 2.60 (t,J=7.0 Hz, 2H), 3.44 (t, J=7.0 Hz, 2H), 4.59 (t, J=5.6 Hz, 1H), 7.34 (d,J=8.5 Hz, 2H), 7.63 (d, J=8.5 Hz, 2H), 11. 55 (s, 1H).

Reference Example 66-(2-Hydroxyethyl)-2,5-dimethyl-3-(2,4,6-trimethoxyphenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0416] White Crystals

Reference Example 73-(1,3-Benzodioxol-5-yl)-6-(2-hydroxyethyl)2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0417] White Crystals

[0418]¹H NMR (400 MHz, DMSO-d₆) δ2.22 (s, 3H), 2.32 (s, 3H), 2.60 (t,J=7.1 Hz, 2H), 3.44 (t, J=7.0 Hz, 2H), 4.58 (t, J=5.6 Hz, 1H), 6.04 (s,2H), 6.81 (d, J=8.1 Hz, 1H), 6.93 (s, 1H), 6.99 (d, J=8.1 Hz, 1H), 11.45(s, 1H)

Reference Example 86-(2-Hydroxyethyl)-2,5-dimethyl-3-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0419] White Crystals

Reference Example 93-(2,4-Dichlorolphenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0420] Brown Crystals

[0421]¹H NMR (400 MHz, DMSO-d₆) δ2.11 (s, 3H), 2.29 (s, 3H), 2.60 (t,J=6.8 Hz, 2H), 3.45 (t, J=6.8 Hz, 2H), 4.2 (br s, 1H), 7.40-7.50 (m,2H), 7.77 (s, 1H).

Reference Example 10 3-(2-Chlorophenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0422] White Crystals

Reference Example 113-(2,4-Dimethoxyphenyl)-6-(2-hydroxyethyl)2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0423] Brown Crystals

[0424]¹H NMR (400 MHz, DMSO-d₆) δ2.12 (s, 3H), 2.30 (s, 3H), 2.59 (t,J=7.2 Hz, 2H), 3.44 (t, J=6.8 Hz, 2H), 3.72 (s, 3H), 3.80 (s, 3H), 6.60(br d, J=8.4 Hz, 1H), 6.64 (br s, 1H), 7.13 (d, J=8.4 Hz, 1H).

Reference Example 126-(2-Hydroxyethyl)-2,5-dimethyl-3-(2-methylphenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0425] White Crystals

[0426]¹H NMR (400 MHz, DMSO-d₆) δ2.06 (s, 3H), 2.08 (s, 3H), 2.29 (s,3H), 2.60 (t, J=6.8 Hz, 2H), 3.46 (t, J=7.2 Hz, 2H), 7.20-7.35 (m, 4H).

Reference Example 136-(2-Hydroxyethyl)-3-(2-methoxy-4-methylphenyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0427] White Crystals

[0428]¹H NMR (400 MHz, DMSO-d₆) δ2.14 (s, 3H), 2.30 (s, 3H), 2.36 (s,3H), 2.60 (t, J=7.2 Hz, 2H), 3.45 (t, J=6.8 Hz, 2H), 3.72 (s, 3H), 6.83(d, J=7.2 Hz, 1H), 6.91 (s, 1H), 7.11 (d, J=7.6 Hz, 1H).

Reference Example 143-(3-Chlorophenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0429] White Crystals

[0430]¹H NMR (400 MHz, DMSO-d₆) δ2.24 (s, 3H), 2.34 (s, 3H), 2.61 (t,J=6.8 Hz, 2H), 3.42-3.49 (m, 2H), 4.59 (br s, 1H), 7.34 (d, J=7.2 Hz,1H), 7.39 (dd, J=1.2, 8.0 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.47 (dd,J=7.6, 8.0 Hz, 1H), 11.61 (s, 1H).

Reference Example 153-(4-Chlorophenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0431] White Crystals

[0432]¹H NMR (400 MHz, DMSO-d₆) δ2.23 (s, 3H), 2.33 (s, 3H), 2.60 (t,J=7.2 Hz, 2H), 3.42-3.49 (m, 2H), 4.59 (br s, 1H), 7.39 (dd, J=2.0, 6.4Hz, 2H), 7.49 (dd, J=2.0 Hz, 6.4, 2H), 11.55 (s, 1H).

Reference Example 163-(2,6-Dimethylphenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0433] Pale Brown Crystals

[0434]¹H NMR (400 MHz, DMSO-d₆); δ1.95 (s, 3H), 1.97 (s, 6H), 2.27 (s,3H), 2.60 (t, J=7.2 Hz, 2H), 3.47 (dt, J=7.2, 5.6 Hz, 2H), 4.59 (t,J=5.6 Hz, 1H), 7.15 (d, J=7.2 Hz, 2H), 7.15-7.22 (m, 1H), 11.47 (s, 1H).

Reference Example 173-(4-Bromo-2-methylphenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0435] White Crystals

[0436]¹H NMR (400 MHz, DMSO-d₆) δ2.07 (s, 6H), 2.28 (s, 3H), 2.59 (t,J=6.7 Hz, 2H), 3.45 (t, J=6.6 Hz, 2H), 4.58 (t, J=5.4 Hz, 1H), 7.14 (d,J=8.1 Hz, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.56 (s, 1H), 11.45 (s, 1H).

Reference Example 183-(2,4-Dimethylphenyl)-6-(2-hydroxyethyl)-2,5-dimethyl-4,7-dihydropyrzolo[1,5-a]pyrimidin-7-one

[0437] White Crystals

[0438]¹H NMR (400 MHz, DMSO-d₆); δ2.06 (s, 3H), 2.07 (s, 3H), 2.30 (s,3H), 2.33 (s, 3H), 2.61 (t, J=7.2 Hz, 2H), 3.47 (dt, J=7.2, 5.6 Hz, 2H),4.59 (t, J=5.6 Hz, 1H), 7.08 (s, 2H), 7.16 (s, 1H), 11.43 (s, 1H).

Reference Example 197-Chloro-6-(2-chloroethyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0439] A mixture of6-(2-hydroxyethyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one(22.7 g, 69.8 mmol), N,N-dimethylaniline (6 drops) and phosphorusoxychloride (45 g) was heated under reflux for three hours. The reactionmixture was poured onto ice (400 g), followed by extracting with ethylacetate. The organic layer was washed with brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (67% ethyl acetate/hexane), to give a crudepurified title compound (9.7 g). The compound was further recrystallizedfrom 50% ethyl acetate/hexane, to give the title compound (5.4 g) aswhite crystals.

[0440]¹H NMR (400 MHz, CDCl₃) δ1.56 (s, 6H), 2.00 (s, 3H), 2.31 (s, 3H),2.34 (s, 3H), 2.60 (s, 3H), 3.32 (t, J=7.6 Hz, 2H), 3.74 (t, J=7.6 Hz,2H), 6.98 (s, 2H).

Reference Example 203-(4-Bromophenyl)-7-chloro-6-(2-chloroethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0441] Pale Yellow Crystals

[0442]¹H NMR (400 MHz, CDCl₃) δ2.64 (s, 3H), 2.69 (s, 3H), 3.33 (t,J=7.5 Hz, 2H), 3.74 (t, J=7.5 Hz, 2H), 7.59 (d, J=1.1 Hz, 2H), 7.59 (d,J=1.1 Hz, 2H).

Reference Example 217-Chloro-6-(2-chloroethyl)-2,5-dimethyl-3-(2,4,6-trimethoxyphenyl)pyrazolo[1,5-a]pyrimidin

[0443] Pale Yellow Crystals

[0444]¹H NMR (400 MHz, CDCl₃) δ2.36 (s, 3H), 2.60 (s, 3H), 3.29 (t,J=7.7 Hz, 2H), 3.70 (t, J=7.7 Hz, 2H), 3.72 (s, 6H), 3.87 (s, 3H), 6.26(s, 2H).

Reference Example 223-(1,3-Benzpdioxol-5-yl)-7-chloro-6-(2-chloroethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0445] Pale Yellow Crystals

[0446]¹H NMR (400 MHz, CDCl₃) δ2.63 (s, 3H), 2.68 (s, 3H), 3.32 (t,J=7.5 Hz, 2H), 3.74 (t, J=7.5 Hz, 2H), 6.00 (s, 2H), 6.93 (d, J=8.0 Hz,1H), 7.11 (dd, J=1.7, 8.0 Hz, 1H), 7.22 (d, J=1.7 Hz, 1H).

Reference Example 233-(4-Bromo-2-methylphenyl)-7-chloro-6-(2-chloroethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0447] Pale Yellow Crystals

[0448]¹H NMR (400 MHz, CDCl₃) δ2.17 (s, 3H), 2.41 (s, 3H), 2.63 (s, 3H),3.33 (t, J=7.5 Hz, 2H), 3.74 (t, J=7.5 Hz, 2H), 7.10 (d, J=8.1 Hz, 1H),7.39 (dd, J=2.1, 8.2 Hz, 1H), 7.49 (d, J=2.2 Hz, 1H).

Reference Example 247-Chloro-6-(2-chloroethyl)-3-(2,4-dimethylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0449] Pale Yellow Crystals

[0450]¹H NMR (400 MHz, CDCl₃) δ2.16 (s, 3H), 2.38 (s, 3H), 2.42 (s, 3H),2.62 (s, 3H), 3.32 (t, J=7.6 Hz, 2H), 3.74 (t, J=7.6 Hz, 2H), 7.08 (d,J=7.6 Hz, 1H), 7.13 (d, J=7.6 Hz, 1H), 7.16 (s, 1H).

Reference Example 257-Chloro-6-(2-chloroethyl)-3-mesityl-5-methylpyrazolo[1,5-a]pyrimidine

[0451]¹H NMR (400 MHz, CDCl₃) δ2.09 (s, 6H), 2.33 (s, 3H), 2.65 (s, 3H),3.35(t, J=7.6 Hz, 2H), 3.77 (t, J=7.6 Hz, 2H), 6.98 (s, 2H), 8.06 (s,1H).

Reference Example 267-Chloro-6-(2-chloroethyl)-2-ethyl-3-mesityl-5-methylpyrazolo[1,5-a]pyrimidine

[0452]¹H NMR (400 MHz, CDCl₃) δ1.16 (t, J=7.6 Hz, 3H), 1.99 (s, 6H),2.34 (s, 3H), 2.59 (s, 3H), 2.67 (q, J=7.6 Hz, 2H), 3.32 (t, J=7.7 Hz,2H), 3.74 (t, J=7.7 Hz, 2H), 6.97 (s, 2H).

Reference Example 27 Ethyl2-(3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)acetate

[0453] Diethyl acetylsuccinate (0.3 mL) and a catalytic amount of4-toluenesulfonic acid monohydrate were added to a solution of4-mesityl-3-methyl-1H-5-pyrazoleamine (100 mg) of Reference Example 1 inxylene (5 mL). Under heating under reflux, the mixture was stirred forthree hours while distilling water off with Dean-Stark. The reactionsolution was cooled, water was added thereto. The mixture was extractedtwice with ethyl acetate, and washed twice with an aqeous saturatedsolution of sodium bicarbonate. The organic layer was separated anddried over anhydrous magnesium sulfate. The solvent was evaporated, andthe residue was purified by silica gel column chromatography, to givethe title compound (200 mg) as a yellow amorphous material.

[0454]¹H NMR (400 MHz, CDCl₃) δ1.27 (t, J=6.8 Hz, 3H), 2.01 (s, 6H),2.06 (s, 3H), 2.22 (s, 3H), 2.35 (s, 3H), 3.57 (s, 2H), 4.16 (q, J=7.2Hz, 2H), 6.81 (s, 2H), 9.84 (s, 1H).

Reference Example 28 Ethyl2-(7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimridin-6-yl)acetate

[0455] Phosphorus oxychloride (1.7 g) was added to ethyl2-(3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)acetate(120 mg) of Reference Example 27 at room temperature, followed bystirring for one hour under heating under reflux. After cooling, thereaction solution was poured onto ice. The reaction mixture was basifiedwith an aqueous saturated solution of sodium bicarbonate, and thenextracted twice with ethylacetate. The organic layer was washed withbrine, and then dried over anhydrous magnesium sulfate. The solvent wasevaporated, to give the title compound (130 mg) as a reddish brown oil.

[0456]¹H NMR (400 MHz, CDCl₃) δ1.29 (t, J=7.2 Hz, 3H), 2.00 (s, 6H),2.31 (s, 3H), 2.34 (s, 3H), 2.52 (s, 3H), 3.88 (s, 2H), 4.22 (q, J=7.2Hz, 2H), 6.98 (s, 2H).

Reference Example 29 Ethyl2-[7-[(1-Ethylpropyl)amino]-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl]acetate

[0457] 3-Aminopentane (0.6 mL) was added to a solution of ethyl2-(7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate(130 mg) in acetonitrile (5 mL), followed by heating under refluxovernight. After cooling the reaction solution, water was added thereto.The mixture was extracted twice with ethylacetate, and the organic layerwas washed with an aqueus saturated solution of sodium bicarbonate, andthen dried over anhydrous magnesium sulfate. The solvent was evaporated,and the residue was purified by silica gel column chromatography, togive the title compound (84 mg) as a green oil.

[0458]¹H NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.2 Hz, 6H), 1.29 (t, J=7.2Hz, 3H), 1.58-1.80 (m, 4H), 2.03 (s, 6H), 2.20 (s, 3H), 2.32 (s, 3H),2.43 (s, 3H), 3.69 (s, 2H) 3.85 (m, 1H), 4.22 (q, J=7.2 Hz, 2H), 6.11(br s, 1H). 6.95 (s, 2H).

Reference Example 306-(2-Hydroxypropyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0459] White Crystals

[0460]¹H NMR (400 MHz, DMSO-d₆) δ1.07 (d, J=6.4 Hz, 3H), 1.93 (s, 3H),1.95 (s, 6H), 2.26 (s, 3H), 2.27 (s, 3H), 2.38-2.41 (m, 1H), 2.52-2.56(m, 1H), 3.82 (m, 1H), 4.50 (d, J=4.8 Hz, 1H), 6.96 (s, 2H), 11.40 (s,1H).

Reference Example 317-Chloro-6-(2-chloropropyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidine

[0461] Yellow Amorphous

[0462]¹H NMR (400 MHz, CDCl₃) δ1.67 (d, J=6.4 Hz, 3H), 2.00 (s, 3H),2.01 (s, 3H), 2.31 (s, 3H), 2.34 (s, 3H), 2.61 (s, 3H), 3.00-3.35 (m,2H), 4.39 (m, 1H), 6.98 (s, 2H).

Reference Example 326-(2-Hydropentyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0463] White Crystals

[0464]¹H NMR (400 MHz, DMSO-d₆) δ0.86 (t, J=6.8 Hz, 3H), 1.26-1.39 (m,3H), 1.39-1.50 (m, 1H), 1.93 (s, 3H), 1.95 (s, 6H), 2.26 (s, 3H), 2.27(s, 3H), 2.35 (dd, J=4.4, 13.6 Hz, 1H), 2.59 (dd, J=8.0, 13.6 Hz, 1H),3.63 (br s, 1H), 4.42 (d, J=5.2 Hz, 1H), 6.96 (s, 2H), 11.39 (s, 1H).

Reference Example 336-(3-Hydroxypropyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0465] White Crystals

[0466]¹H NMR (400 MHz, DMSO-d₆) δ1.57 (tt, J=7.6, 7.2 Hz, 2H), 1.93 (s,6H), 1.95 (s, 3H), 2.25 (s, 3H), 2.27 (s, 3H), 2.45 (t, J=8.0 Hz, 1H),3.38-3.43 (m, 2H), 4.38 (t, J=5.6 Hz, 1H), 6.96 (s, 2H), 11.40 (s, 1H).

Reference Example 343-Bromo-6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol

[0467] A solution of 5-amino-4-bromo-3-methylpyrazole hydrobromide (13g, 51 mmol) and α-acetyl-γ-butyrolactone (6.8 g, 53 mmol) in ethanol (65mL) was heated under reflux for nine hours. After cooling to roomtemperature, the resulting crystals were collected by filtration, togive the title compound (4.6 g) as white crystals.

[0468]¹H NMR (400 MHz, DMSO-d₆) δ2, 24 (s, 3H), 2.39 (s, 3H), 2.97 (t,J=7.6 Hz, 2H), 3.56 (t, J=7.6 Hz, 2H).

Reference Example 353-Bromo-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0469] Phosphorus oxychloride (3.3 mL) was added to a solution of3-bromo-6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol(1.0 mg, 3.50 mmol) in N,N-dimethyaniline (5 mL), followed by stirringat 120° C. for 20 minutes. After cooling to room temperature, themixture was added dropwise slowly into ice-water under vigorouslystirring. Then, the mixture was stirred for two hours while raising atemperature gradually to room temperature, followed by diluting withethyl acetate. The organic layer was washed with brine, dried overanhydrous magnesium sulfate and evaporated. 3-Aminopentane (10 mL) wasadded to a solution of the residue in acetonitrile (30 mL), followed byheating under reflux for three hours. The mixture was diluted withethylacetate, and the organic layer was washed with water and brine,dried over anhydrous magnesium sulfate and evaporated. The resultingcrystals were collected by filtration, to give the title compound (700mg) as white crystals.

[0470]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.6 Hz, 6H), 1.50-1.68 (m,4H), 2.37 (s, 3H), 2.39 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.67 (t, J=9.2Hz, 2H), 5.50-5.60 (m, 1H).

Reference Example 366-(2-Hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol

[0471] A solution of 3-amino-5-methylpyrazole (25.0 g, 0.26 mole),α-acetyl-γ-butyrolactone (34.5 g, 0.27 mmol) and acetic acid (5 mL) intoluene (350 mL) was heated under reflux for three hours. After coolingto room temperature, the resulting crystals were collected by filtrationand washed with ethyl acetate, to give the title compound (48.0 g) aswhite crystals.

[0472]¹H NMR (400 MHz, DMSO-d₆) δ2.24 (s, 3H), 2.29 (s, 3H), 2.57 (t,J=6.8 Hz, 2H), 3.42 (t, J=6.8 Hz, 2H), 5.83 (s, 1H).

Reference Example 377-Chloro-6-(2-chloroethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0473] A solution of6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol (10.0 g, 48mmol) and phosphorus oxychloride (45 mL, 0.48 mol) inN,N-dimethylaniline (50 mL) was stirred at room temperature for 30minutes and further at 120° C. for one hour. After cooling to roomtemperature, the mixture was added dropwise into ice-water whilestirring vigorously. The mixture was stirred for two hours whilegradually raising a temperature to room temperature. The mixture wasdiluted with ethyl acetate, and the organic layer was washed with brine,dried over magnesium anhydrous sulfate and evaporated. The residue waspurified by silica gel column chromatography (10% ethyl acetate/hexane),to give the title compound (6.5 g) as white crystals.

[0474]¹H NMR (400 MHz, CDCl₃) δ2.54 (s, 3H), 2.67 (s, 3H), 3.31 (t,J=7.6 Hz, 2H), 3.72 (t, J=7.6 Hz, 2H), 6.44 (s, 1H).

Reference Example 388-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidine

[0475] A solution of7-chloro-6-(2-chloroethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine (4.0 g,16 mmol), 3-aminopentane (40 mL) in acetonitryl (120 mL) was heatedunder reflux for nine hours. After evaporating, the residue was purifiedby silica gel column chromatography (20% ethyl acetate/hexane), to givethe title compound (3.7 g) as white crystals.

[0476]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.6 Hz, 6H), 1.50-1.65 (m,4H), 2.31 (s, 3H), 2.39 (s, 3H), 3.07 (t, J=9.2 Hz, 2H), 3.65 (t, J=9.2Hz, 2H), 5.53-5.63 (m, 1H), 6.02 (s, 1H).

Reference Example 398-(1-Ethylpropyl)-3-iodo-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0477] N-Iodosuccinimide (3.5 g, 15 mmol) was added to a solution of8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(3.7 g 15 mmol) in N,N-dimethylformamide (40 mL) at room temperature,followed by stirring for one hour. Hypo water was added, and the mixturewas diluted with ethyl acetate, washed with an aqueous saturatedsolution of ammonium chloride and brine, dried over anhydrous magnesiumsulfate and evaporated. The residue was purified by silica gel columnchromatgraphy (20-40% ethyl acetate/hexane) to give the title compound(4.37 g) as white crystals.

[0478]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.6 Hz, 6H), 1.48-1.66 (m,4H), 2.37 (s, 3H), 2.40 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.67 (t, J=9.2Hz, 2H), 5.48-5.60 (m, 1H).

Reference Example 40 8-(1-Ethylpropyl)-3-(1-ethynyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrmidine

[0479] A solution of8-(1-ethylpropyl)-3-iodo-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(2.0 g, 5.29 mmol), trimethylsilylacetylene(0.8 mL, 5.82 mmol),Cl₂Pd(PPh₃)₂ (0.19 g, 0.26 mmol) and copper (I) iodide (50 mg, 0.26mmol) in triethylamine (20 mL) was stirred at room temperature for twohours. The solution was filtered through Celite, and the filtrate wasevaporated. Tetramethylammonium fluoride (1.0 M tetrahydrofuran solution6.3 mL, 6.3 mmol) was added to a solution of the residue intetrahydrofuran (20 mL) at room temperature, followed by stirring for 10minutes. Water was added thereto, and the mixture was diluted with ethylacetate, washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(10-20% ethyl acetate/hexane), to give the title compound (727 mg) aspale brown crystals.

[0480]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.6 Hz, 6H), 1.50-1.68 (m,4H), 2.37 (s, 3H), 2.45 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.40 (s, 1H),3.67 (t, J=9.2 Hz, 2H), 5.48-5.60 (m, 1H).

Reference Example 412-2-[8-(1-Ethynylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-1-ethynylaniline

[0481] A solution of8-(1-ethylpropyl)-3-(1-ethynyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(600 mg, 2.13 mmol), 2-iodoaniline (465 mg, 2.13 mmol), Cl₂Pd(PPh₃)₂ (75mg, 0.11 mmol) and copper (I) iodide (20 mg, 0.11 mmol) in triethylamine(6 mL) and N,N-dimethylformamide (3 mL) was stirred at room temperaturefor three hours. The solution was filtered through Celite, and thefiltrate was evaporated. The residue was purified by silica gel columnchromatography (30-50% ethyl acetate/hexane), to give the title compound(540 mg) as white crystals.

[0482]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.6 Hz, 6H), 1.50-1.70 (m,4H), 2.36 (s, 3H), 2.50 (s, 3H), 3.10 (t, J=9.2 Hz, 2H), 3.68 (t, J=9.2Hz, 2H), 4.33-4.50 (m, 2H), 5.50-5.61 (m, 1H), 6.68 (dd, J=7.6 Hz, 1.2Hz, 1H), 6.70 (dt, J=7.6 Hz, 1.2 Hz, 1H), 7.07 (dt, J=7.6 Hz, 1.2 Hz,1H), 7.39 (dd, J=7.6 Hz, 1.2 Hz, 1H).

Reference Example 428-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-carbaldehyde

[0483] Phosphorus oxychloride (5.5 mL, 60 mmol) was added to a solutionof8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[[3,2-e]pyrimidine(5.0 g, 20 mmol) in N,N-dimethylformamide (25 mL) at room temperature,followed by stirring for one hour. The reaction solution was pouredslowly into a 2N aqueous solution of sodium hydroxide, followed bystirring at room temperature for 30 minutes. The reaction mixture wasextracted with ethyl acetate, washed with brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (50-70% ethyl acetate/hexane), to give the titlecompound (6.48 g) as white crystals.

[0484]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.6 Hz, 6H), 1.50-1.69 (m,4H), 2.37 (s, 3H), 2.62 (s, 3H), 3.13 (t, J=9.2 Hz, 2H), 3.71 (t, J=9.2Hz, 2H), 5.48-5.60 (m, 1H), 10.19 (s, 1H).

Reference Example 43 Ethyl7-amino-3-mesityl-2,5-dimethylpyrazolo[1,5-a]primidin-6-carboxylate

[0485] Concentrated hydrochloric acid (0.1 mL) was added to a solutionof 4-mesityl-3-methyl-1H-5-pyrazoleamine (2.5 g, 11.61 mmol) and ethyl2-cyano-3-ethoxy-2-butenoate (2.13 g, 11.61 mmol) in methanol (30 mL),followed by heating under reflux for 18 hours. The reaction mixture wasevaporated as it was. Then, water was added and a 5N aqueous solution ofsodium hydroxide was added under ice-cooling, to neutralize. Further,the mixture was extracted with ethyl acetate, and the organic layer waswashed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(15% ethyl acetate/hexane), to give the title compound (835 mg).

[0486]¹H NMR (400 MHz, CDCl₃) δ1.41 (t, J=7.1 Hz, 3H), 2.02 (s, 6H),2.21 (s, 3H), 2.32 (s, 3H), 2.68 (s, 3H), 4.39 (q, J=7.1 Hz, 2H), 6.95(s, 2H).

Reference Example 44 Ethyl3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-carboxylate

[0487] Acetic acid (5 mL) was added to a solution of4-mesityl-3-methyl-1H-5-pyrazoleamine (5 g, 23.22 mmol) and diethyl2-acetylmalonate (4.7 g, 23.22 mmol) in xylene (40 mL), followed byheating under reflux for seven hours. The reaction mixture wasevaporated as it was, and water was added thereto. After extracting withethyl acetate, the organic layer was washed with an aqueous saturatedsodium bicarbonate and brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(20% ethyl acetate/hexane), to give the title compound (3 g).

[0488]¹H NMR (400 MHz, CDCl₃) δ1.39 (t, J=7.1 Hz, 3H), 2.00 (s, 6H),2.13 (s, 3H), 2.33 (s, 3H), 2.75 (s, 3H), 4.41 (q, J=7.1 Hz, 2H), 6.96(s, 2H), 8.20 (br s, 1H).

Reference Example 45 Ethyl7-chloro-3mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate

[0489] Five droplets of N,N-dimethylaniline was added to a solution ofethyl3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-carboxylate(3 g, 8.49 mmol) in phosphorus oxychloride (80 g), followed by heatingunder reflux for four hours. The reaction mixture was added to ice andstirred for a while. Then, the mixture was extracted with ethyl acetate,and the organic layer was washed with an aqueous saturated solution ofsodium bicarbonate and brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(15-30% ethyl acetate/hexane), to give the title compound (1.94 g).

[0490]¹H NMR (400 MHz, CDCl₃) δ1.44 (t, J=7.3 Hz, 3H), 1. 97 (s, 6H), 2.29 (s, 3H), 2.33 (s, 3H), 2.86 (s, 3H), 4.47 (q, J=7.1 Hz, 2H), 6.96 (s,2H).

Reference Example 463-Chloro-6-mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine

[0491] Methylhydrazine (1 mL) was added to a solution of ethyl7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(209 mg, 0.562 mmol) in ethanol (5 mL), followed by stirring at roomtemperature for two hours. The reaction mixture was evaporated as itwas. Two droplets of N,N-dimethylaniline was added to a solution of theresulting crude compound in phosphorus oxychloride (14 g), followed byheating under reflux for five hours. The reaction mixture was added toice, followed by stirring for a while. Then, the mixture was extractedwith ethyl acetate, and the organic layer was washed with an aqueoussaturated solution of sodium bicarbonate and brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (12% ethyl acetate/hexane), to give the titlecompound (14 mg).

[0492]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.34 (s, 3H), 2.37 (s, 3H),3.28 (s, 3H), 3.87 (s, 3H), 7.01 (s, 2H).

Reference Example 47 Ethyl7-cyano-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carhoxylate

[0493] Tetrakis(triphenylphosphine)palladium (0) (691 mg, 0.592 mmol)and zinc cyanide (402 mg, 3.25 mmol) were added to a solution of ethyl7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(1.1 g, 2.96 mmol) in N,N-dimethylformamide (10 mL), followed bystirring at 150° C. for four hours. Water was added to the reactionmixture, and the mixture was extracted with ethyl acetate. The organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated, and the residue was purified by silica gel columnchromatography (15% ethyl acetate/hexane), to give the title compound (1g).

[0494]¹H NMR (400 MHz, CDCl₃) δ1.49 (t, J=7.1 Hz, 3H), 1.96 (s, 6H),2.35 (s, 3H), 2.36 (s, 3H), 3.13 (s, 3H), 4.52 (q, J=7.1 Hz, 2H), 7.00(s, 2H).

Reference Example 483-Mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6,7-dicarboxylic acid

[0495] Potassium hydroxide (441 mg, 11.04 mmol) was added to a solutionof ethyl7-cyano-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(800 mg, 2.21 mmol) in ethanol (15 mL), followed by heating under refluxfor two hours. The reaction mixture was evaporated, water was added.Under ice-cooling, 2N hydrochloric acid was added to adjust the pH ofthe mixture to pH 1. The mixture was extracted with ethyl acetate, andthe organic layer was washed with brine, dried over anhydrous magnesiumsulfate and evaporated, to give the title compound (780 mg).

[0496]¹H NMR (400 MHz, CDCl₃) δ1.96 (s, 6H), 2.37 (s, 6H), 3.01 (s, 3H),7.01 (s, 2H).

[0497] MS (ESI) m/z 354 MH⁺

Reference Example 49 6-(3-Hydroxyhexyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one

[0498] 3-Amino-4-mesityl-5-methylpyrazole (2 g, 9.29 mmol) and2-acetyl-5-propylpropiolactone (2.05 g, 11.1 mmol) were suspended inxylene (40 mL), followed by heating under reflux for 16 hours. Aftercooling, the resulting crystals were collected by filtration, washedwith diethyl ether and then dried under reduced pressure, to give thetile compound (1.54 g, 4.04 mmol) as a white solid.

[0499]¹H NMR (400 MHz, DMSO-d₆) δ0.85 (t, J=7.6 Hz, 3H), 1.30-1.55 (m,4H), 1.93 (s, 6H), 1.95 (s, 3H), 2.24 (s, 3H), 2.27 (s, 3H), 2.30-2.60(m, 4H), 3.35-3.45 (m, 1H), 6.95 (s, 2H).

Reference Example 507-Chloro-6-(3-chlorohexyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine

[0500]6-(3-Hydroxyhexyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one(900 mg, 2.36 mmol) was dissolved in toluene (9 mL). Thionyl chloride(0.18 mL, 2.48 mmol) was added thereto, followed by stirring at 80° C.for one hour. The resulting crystals were collected by filtration,washed with toluene and then dried under reduced pressure, to give awhite solid. The solid was dissolved in phosphorus oxychloride (4 mL).N,N-Dimethylaniline (0.4 mL) was added thereto, followed by heatingunder reflux for 2 hr. After evaporating phosphorus oxychloride, waterwas added to the residue. The mixture was extracted with ethyl acetate,and the organic layer was washed successively with an aqueous saturatedsolution of sodium bicarbonate, water and brine, dried over anhydrousmagnesium sulfate and then evaporated, to give the title compound (850mg, 2.03 mmol) as a pale yellow oil.

[0501]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 3H), 1.42-1.55 (m,1H), 1.56-1.66 (m, 1H), 1.72-1.84 (m, 2H), 1.88-1.99 (m, 1H), 1.99 (s,6H), 2.00-2.10 (m, 1H), 2.30 (s, 3H), 2.34 (s, 3H), 2.58 (s, 3H),2.86-2.96 (m, 1H), 3.08-3.17 (m, 1H), 4.00-4.08 (m, 1H), 6.98 (s, 2H).

Reference Example 512-(3-Mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)acetaldehyde

[0502] Des Martin reagent was added gradually to a solution of6-(2-hydroxyethyl)-3-mesityl-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one(2.65 g, 8.14 mmol) in dichloromethane (200 mL) at room temperature,followed by stirring for three hours. A saturated solution of sodiumthiosulfate was added to the reaction mixture, extracted with ethylacetate, dried over anhydrous magnesium sulfate and evaporated. Theresidue was purified by silica gel column chromatography (50% ethylacetate/hexane, 10% ethyl acetate/methanol), to give the title compound(1.78 g) as a yellow amorphous.

[0503]¹H NMR (400 MHz, CDCl₃) δ2.01 (s, 6H), 2.05 (s, 3H), 2.19 (s, 3H),2.34 (s, 3H), 3.60 (s, 2H), 6.76 (s, 2H), 9.64 (s, 1H).

Reference Example 52 Ethyl4-(3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)butanoate

[0504] In nitrogen stream, sodium hydride (900 mg, 22.5 mmol) was addedto a solution of triethyl phosphonoacetate (5.9 mL, 29.7 mmol) indimethyl formamide (150 ml), followed by stirring at room temperaturefor 10 minutes. Thereafter,2-(3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)acetaldehyde(2.4 g, 7.4 mmol) was added, followed by stirring at room temperaturefor two hours. Water was added to the reaction mixture, extracted withethyl acetate, dried over anhydrous magnesium sulfate and evaporated.The residue was purified by silica gel column chromatography (25-100%ethyl acetate/hexane), to give an olefin compound (2.5 g). The productwas dissolved in methanol (200 mL) and water-containing palladium-carbonwas added, followed by stirring in hydrogen atmosphere for three days.After filtering through Celite, the mixture was evaporated and theresidue was washed with diethyl ether, to give the title compound (1.2g) as white crystals.

[0505]¹H NMR (400 MHz, CDCl₃) δ1.25 (t, J=7.2 Hz, 3H), 1.80-1.90 (m,2H), 2.01 (s, 6H), 2.10 (s, 3H), 2.26 (s, 3H), 2.36 (s, 3H), 2.40 (t,J=7.2 Hz, 2H), 2.57 (dd, J=7.6, 9.6 Hz, 2H), 4.11 (q, J=7.2 Hz, 2H),6.87 (s, 2H), 9.02 (br s, 1H)

Reference Example 53 Ethyl4-(7-butyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)butanoate

[0506] Phosphoeus oxychloride (11.3 g) and N,N-dimethylaniline (3droplets) were added to ethyl4-(3-mesityl-2,5-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)butanoate(700 mg, 1.77 mmol), followed by heating under reflux for 1.5 hours.After the reaction, it was treated with ice-water, neutralized withpotassium carbonate, extracted with ethyl acetate, dried over anhydrousmagnesium sulfate and evaporated. The resulting reaction residue wasdissolved in acetonitrile (5 ml) and n-butylamine (2 mL) was added,followed by heating under reflux for six hours. After the reaction, itwas treated with water, and then neutralized with potassium carbonate,extracted with ethyl acetate, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(10-25% ethyl acetate/hexane), to give the title compound (2.5 g) as ayellow oil.

[0507]¹H NMR (400 MHz, CDCl₃) δ1.01 (t, J=7.6 Hz, 3H), 1.28 (dt, J=0.8,7.6 Hz, 3H), 1.50-1.55 (m, 2H), 1.72-1.82 (m, 2H), 1.82-1.92 (m, 2H),2.02 (s, 6H), 2.20 (s, 3H), 2.31 (s, 3H), 2.44 (t, J=7.2 Hz, 2H), 2.45(s, 3H), 2.71-2.76 (m, 2H), 3.74 (dd, J=6.8, 13.2 Hz, 2H), 4.17 (q,J=7.2 Hz, 2H), 6.26 (t, J=5.6 Hz, 2H), 6.94 (s, 2H).

Reference Example 544-(7-(Butyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-yl)-1-butanol

[0508] A 1.0M solution of diisobutylaluminium hydride in hexane wasadded dropwise into a solution of ethyl4-(7-(butyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)butanoate(320 mg, 0.71 mmol) in tetrahydrofuran (10 mL) under nitrogen stream,followed by stirring for 30 minutes. After Celite was added, the mixturewas treated by adding ethyl acetate and water dropwise, and theinsoluble matters were filtered off. The solution was extracted withethyl acetate, dried over anhydrous magnesium sulfate and evaporated, togive the title compound (320 mg) as a brown oil.

[0509]¹H NMR (400 MHz, CDCl₃) δ1.01 (s, 3H), 1.46-1.57 (m, 2H),1.60-1.70 (m, 3H), 1.72-1.83 (m, 3H), 2.02 (s, 6H), 2.20 (s, 3H), 2.31(s, 3H), 2.45 (s, 3H), 2.71-2.76 (m, 2H), 3.60-3.71 (m, 4H), 6.25 (t,J=5.2 Hz, 1H), 6.94 (s, 2H).

Reference Example 55N-Butyl-N-(6-(4-chlorobutyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)amine

[0510] Phosphorus oxychloride (11.3 g) and N,N-dimethylaniline (3droplets) were added to4-(7-(butyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-1-butanol(320 mg, 0.78 mmol), followed by heating under reflux for 0.5 hour.After the reaction, the mixture was treated with ice-water, neutralizedwith potassium carbonate, extracted with ethyl acetate, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (10-15% ethyl acetate/hexane), to givethe title compound (254 mg) as a pale yellow oil.

[0511]¹H NMR (400 MHz, CDCl₃) δ1.02 (t, J=7.6 Hz, 3H), 1.48-1.58 (m,2H), 1.60-1.84 (m, 4H), 1.86-1.96 (m, 2H), 2.02 (s, 6H), 2.20 (s, 3H),2.32 (s, 3H), 2.46 (s, 3H), 2.74 (t, J=8.0 Hz, 2H), 2.60-3.67 (m, 4H),6.26 (t, J=5.6 Hz, 1H), 6.95 (s, 2H).

Reference Example 563-((E)-1-[3-Methyl-1-(2,4,6-trichlorophenyl)-1H-5-pyrazolyl]aminoethylidene)tetrahydro-2-furanone

[0512] 3-Amino-2-(2,4,6-trichlorophenyl)-5-methylpyrazole (1 g, 3.62mmol) was dissolved in ethanol (10 mL). α-Acetyl-γ-butyrolactone (0.409mL, 3.80 mmol) was added, followed by heating under reflux for two days.After ethanol was evaporated, the residue was purified by silica gelcolumn chromatography (10% ethyl acetate/hexane), to give the titlecompound (700 mg, 1.80 mmol) as a pale yellow oil.

[0513]¹H NMR (400 MHz, CDCl₃) δ2.06 (s, 3H), 2.33 (s, 3H), 2.85 (t,J=8.0 Hz, 2H), 4.30 (t, J=8.0 Hz, 2H), 5.90 (s, 1H), 7.47 (s, 2H), 9.77(brs, 1H).

Reference Example 574-Chloro-5-(2-chloroethyl)-3,6-dimethyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-b]pyridine

[0514]3-((E)-1-[3-Methyl-1-(2,4,6-trichlorophenyl)-1H-5-pyrazolyl]aminoethylidene)tetrahydro-2-furanone(500 mg, 1.29 mmol) was dissolved in phosphorus oxychloride (4 mL), andheated under reflux for two hours. After phosphorus oxychloride wasevaporated, water was added to the residue. The mixture was extractedwith ethyl acetate, and the organic layer was washed with an aqueoussaturated solution of sodium bicarbonate, water and brine, dried overanhydrous magnesium sulfate, and then evaporated. The residue waspurified by silica gel column chromatography (10% ethyl acetate/hexane),to give the title compound (166 mg, 0.392 mmol) as a pale yellow oil.

[0515]¹H NMR (400 MHz, CDCl₃) δ2.66 (s, 3H), 2.79 (s, 3H), 3.39 (t,J=8.0 Hz, 2H), 3.72 (t, J=8.0 Hz, 2H), 7.52 (s, 2H).

Reference Example 58 5-Mesityl-2-methyl-4-nitro-1H-imidazole

[0516] A solution of 5-bromo-2-methyl-4-nitroimidazole (5.0 g, 24 mmol),mesitylboric acid (3.96 g, 24 mmol), Pd(PPh₃)₄ (1.4 g, 1.2 mmol) andbarium hydroxide octahydrate (19.1 g, 61 mmol) in 2,2-dimethoxyethane(150 mL) and water (25 mL) was heated at reflux for four hours. Afterfiltered through Celite, the filtrate was diluted with ethyl acetate,washed with brine, dried over anhydrous magnesium sulfate andevaporated. The resulting crystals were washed with ethyl acetate, togive the title compound (4.17 g) as white crystals.

[0517]¹H NMR (400 MHz, DMSO-d₆) δ1.97 (s, 6H), 2.27 (s, 3H), 2.33 (s,3H), 6.97 (s, 2H).

Reference Example 593-(2-Hydroxyethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidin-4-ol

[0518] A solution of 5-mesityl-2-methyl-4-nitro-1H-imidazole (2.1 g,8.56 mmol), α-acetyl-γ-butyrolactone (1.21 g, 9.42 mmol), and ironpowder (2.39 g, 42.8 mmol) in ethanol (40 mL) and acetic acid (10 mL)was stirred at 80° C. for one day. The mixture was filtered throughCelite and evaporated. The resulting crystals were washed with ethylacetate, to give the title compound (0.95 g) as white crystals.

[0519]¹H NMR (400 MHz, DMSO-d₆) δ2.05 (s, 6H), 2.30 (s, 6H), 2.71 (t,J=6.8 Hz, 2H), 2.85 (s, 3H), 3.68 (t, J=6.8 Hz, 2H), 6.95 (s, 2H).

Reference Example 603-(2-chlorethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidin-4-ol

[0520] Thionyl chloride (112 mL, 1.54 mmol) was added to a solution of3-(2-hydroxyethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidin-4-ol(500 mg, 1.54 mmol) in toluene (5 mL) at 80° C., followed by stirringfor one hour. After cooling to room temperature, the resulting crystalswere washed with diethyl ether, to give the title compound (360 mg) aspale brown crystals.

[0521]¹H NMR (400 MHz, CD₃OD) δ2.15 (s, 6H), 2.35 (s, 3H), 2.40 (s, 3H),3.00 (t, J=6.8 Hz, 2H), 3.09 (s, 3H), 3.76 (t, J=6.8 Hz, 2H), 7.08 (s,2H).

Reference Example 614-Chloro-3-(2-chloroethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidine

[0522] A solution of3-(2-chloroethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidin-4-ol(200 mg, 0.58 mmol) and N,N-dimethylaniline (0.3 mL) in phosphorusoxychloride (3 mL) was heated under reflux for six hours. Afterevaporating, 3-aminopentane (2 mL) was added to a solution of theresidue in acetonitrile (5 mL), followed by stirring at 80° C. for threehours. Water was added, and the mixture was extracted with ethylacetate, washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(10-20% ethyl acetate/hexane), to give the title compound (139 mg) aspale yellow crystals.

[0523]¹H NMR (400 MHz, CDCl₃) δ2.08 (s, 6H), 2.30 (s, 3H), 2.48 (s, 3H),3.05 (s, 3H), 3.21 (t, J=7.6 Hz, 2H), 3.71 (t, J=7.6 Hz, 2H), 6.92 (s,2H).

Reference Example 62 4-Chloro-3-(2-chloroethyl)-8-iodo-2-methylquinoline

[0524] 2-Iodoaniline (25 g, 114 mmol) and α-acetyl-γ-butyrolactone (43.8g, 342 mmol) were dissolved in ethanol (250 mL), followed by heatingunder reflux for two days. The solvent was removed, and diethyl etherwas added for crystallization. The crystals were collected by filtrationand dried under reduced pressure, to give a pale yellow solid (28 g).This was dissolved in phosphorus oxychloride (60 mL), followed byheating under reflux for three hours. After phosphorus oxychloride wasevaporated, water was added to the residue, and extracted with ethylacetate. The organic layer was washed with an aqueous saturated solutionof sodium bicarbonate, water and brine, dried over anhydrous magnesiumsulfate, and then evaporated. The residue was purified by silica gelcolumn chromatography (3% ethyl acetate/hexane), to give the titlecompound (19 g, 50.0 mmol) as brown crystals.

[0525]¹H NMR (400 MHz, CDCl₃) δ2.90 (s, 3H), 3.50 (t, J=7.6 Hz, 3H),3.76 (t, J=7.6 Hz, 3H), 7.28 (t, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H),8.33 (d, J=8.0 Hz, 1H).

Reference Example 631-(1-Ethylpropyl)-6-iodo-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline

[0526] 4-Chloro-3-(2-chloroethyl)-8-iodo-2-methylquinoline (900 mg, 2.46mmol) was dissolved in 3-aminopentane (10 mL), followed by addingp-toluenesulfonic acid (900 mg). The mixture was sealed at 200° C. forsix hours. Water was added to the reaction mixture, extracted with ethylacetate, and the organic layer was washed with water and brine, driedover magnesium sulfate, and then evaporated. The residue was purified bysilica gel column chromatography (10% ethyl acetate/hexane), to give thetitle compound (450 mg, 1.18 mmol) as white crystals.

[0527]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.48-1.70 (m,4H), 2.55 (s, 3H), 3.08 (t, J=9.6 Hz, 3H), 3.70 (t, J=9.6 Hz, 3H),4.18-4.26 (m, 1H), 6.92 (dd, J=7.6, 8.4 Hz, 1H), 8.02 (dd, J=1.0, 8.4Hz, 1H), 8.16 (dd, J=1.0, 7.6 Hz, 1H).

Reference Example 641-(1-Ethylpropyl)-6-iodo-4-methyl-1-H-pyrrolo[3,2-c]quinoline

[0528]1-(1-Ethylpropyl)-6-iodo-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline(450 mg, 1.18 mmol) was dissolved in toluene (10 mL). To the mixture wasadded activated manganese dioxide (4.95 g), followed by heating at 40°C. overnight. The reaction mixture was filtered through Celite andwashed with ethyl acetate. The filtrate was evaporated, and the residuewas purified by silica gel column chromatography (5% ethylacetate/hexane), to give the title compound (334 mg, 0.884 mmol) as awhite oil.

[0529]¹H NMR (400 MHz, CDCl₃) δ2.90 (s, 3H), 3.50 (t, J=7.6 Hz, 3H),3.76 (t, J=7.6 Hz, 3H), 7.28 (t, J=8.0 Hz, 3H), 8.19 (d, J=8.0 Hz, 3H),8.33 (d, J=8.0 Hz, 3H).

Reference Example 65 2-Mesityl-3-nitropyridine

[0530] A solution of2-chloro-3-nitropyridine (5.0 g, 31.5 mmol),mesitylboric acid (5.65 g, 34.7 mmol), Pd(PPh₃)₄ (1.82 g, 1.58 mmol) andbarium hydroxide octahydrate (14.9 g, 47.3 mmol) in 2,2-dimethoxyethane(150 mL) and water (25 mL) was heated under reflux for one day. Themixture was filtered through Celite, and the filtrate was diluted withethyl acetate, washed with brine, dried over anhydrous magnesium sulfateand evaporated. The residue was purified by silica gel columnchromatography (10% ethyl acetate/hexane), to give the title compound(5.99 g) as pale yellow oil.

[0531]¹H NMR (400 MHz, CDCl₃) δ1.95 (s, 6H), 2.32 (s, 3H), 6.92 (s, 2H),7.51 (dd, J=8.0 Hz, 4.8 Hz, 1H), 8.31 (dd, J=8.0 Hz, 1.2 Hz, 1H), 8.36(dd, J=4.8 Hz, 1.2 Hz, 1H).

Reference Example 66 2-Mesityl-3-pyridinamine

[0532] Palladium-carbon (10%, 0.6 g) was added to a solution of2-mesityl-3-nitropyridine (5.99 g, 23 mmol) in ethanol (120 mL),followed by stirring for one day in hydrogen atmospher. The mixture wasfiltered through Celite and evaporated, to give the title compound (5.2g) as white crystals.

[0533]¹H NMR (400 MHz, CDCl₃) δ2.01 (s, 6H), 2.31 (s, 3H), 6.94 (s, 2H),7.05 (dd, J=8.0 Hz, 1.6 Hz, 1H), 7.08 (dd, J=8.0 Hz, 4.4 Hz, 1H), 8.36(dd, J=4.4 Hz, 1.6 Hz, 1H).

Reference Example 673-1-[(2-Mesityl-3-pyridyl)amino]ethylidenetetrahydro-2-furanone

[0534] p-Toluenesulfonic acid monohydrate (39 mg, 0.20 mmol) was addedto a solution of 2-mesityl-3-pyridinamine (3.9 g, 18mmol) andα-acetyl-γ-butyrolactone (4.7 g, 37 mmol) in toluene (80 mL). Themixture was heated under reflux for seven days while removing waterusing Dean-Stark apparatus. The mixture was evaporated, and theresulting crystals were washed with 60% diethyl ether/ethyl acetate, togive the title compound (3.74 g) as white crystals.

[0535]¹H NMR (400 MHz, CDCl₃) δ1.97 (s, 6H), 2.03 (s, 3H), 2.29 (s, 3H),2.82 (t, J=7.6 Hz, 2H), 4.26 (t, J=7.6 Hz, 2H), 6.93 (s, 2H), 7.25 (dd,J=8.0 Hz, 4.8 Hz, 1H), 7.41 (dd, J=8.0 Hz, 1.2 Hz, 1H), 8.46 (dd, J=4.8Hz, 1.2 Hz, 1H), 9.46 (s, 1H).

Refernce Example 684-Chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,7]naphthyridine

[0536] A solution of3-1-[(2-mesityl-3-pyridyl)amino]ethylidenetetrahydro-2-furanone (2.0 g,6.20 mmol) in phosphorus oxychloride (8.0 mL) was stirred at 120° C. forone hour. After cooling to room temperature, the mixture was slowlyadded dropwise into ice-water while stirring vigorously and stirred forone hour while raising a temperature to room temperature. The mixturewas diluted with ethyl acetate, and the organic layer was washed withbrine, dried over anhydrous magnesium sulfate and evaporated. Theresidue was purified by silica gel column chromatography (0-2% ethylacetate/hexane), to give the title compound (500 mg) as white crystals.

[0537]¹H NMR (400 MHz, CDCl₃) δ1.87 (s, 6H), 2.36 (s, 3H), 2.71 (s, 3H),3.50 (t, J=7.6 Hz, 2H), 3.79 (t, J=7.6 Hz, 2H), 6.96 (s, 2H), 7.96 (d,J=6.0 Hz, 1H), 8.73 (d, J=6.0 Hz, 1H).

Reference Example 69 tert-Butyl N-(3-pyridyl)carbamate

[0538] Sodium bis(trimethylsilyl)amide (1.0M tetrahydrofuran solution800 mL, 0.80M) was added to a solution of 3-aminopyridine (34.2 g, 0.36mmol) in tetrahydrofuran (800 mL), followed by stirring for two hours. Asolution of di-tert-butyl dicarbonate in tetrahydrofuran (200 mL) wasadded thereto and stirred for 30 minutes. Water was added, extractedwith ethyl acetate, and the organic layer was washed with 1Nhydrochloric acid, water and brine, dried over anhydrous magnesiumsulfate and evaporated. The resulting crystals were washed with hexane,to give the title compound (55.0 g) as white crystals.

[0539]¹H NMR (400 MHz, CDCl₃) δ1.52 (s, 9H), 6.85 (br s, 1H), 7.24 (ddd,J=8.4 Hz, 4.8 Hz, 0.8 Hz, 1H), 7.95-8.04 (m, 1H), 8. 28 (dd, J=4.8 Hz,1.6 Hz, 1H), 8.35 (dd, J=2.8 Hz, 0.8 Hz, 1H).

Reference Example 70 tert-Butyl N-(4-iodo-3-pyridyl)carbamate

[0540] N-Butyllithium (1.6M hexane solution 400 mL, 0.64 mol) was addedto a solution of tert-butyl N-(3-pyridyl)carbamate (51.8 g, 0.27 mol)and tetramethylethylenediamine (96.6 mL, 0.64 ml) in diethyl ether (1.5L) at −78° C., followed by stirring at −20° C. for 2.5 hr. After coolingto −78° C. again, a solution of iodine (94.8 g, 0.37 mol) in diethylether (200 mL) was added and stirred for one day while raising atemperature to room temperature. Water was added, extracted with diethylether, and the organic layer was washed with hypo-water and brine, driedover anhydrous magnesium sulfate and evaporated. The resulting crystalswere washed with hexane, to give the title compound (53.0 g) as whitecrystals.

[0541]¹H NMR (400 MHz, CDCl₃) δ1.54 (s, 9H), 6.67 (br s, 1H), 7.69 (d,J=4.8 Hz, 1H), 7.90 (d, J=4.8 Hz, 1H), 9.14 (s, 1H).

Reference Example 71 tert-Butyl N-(4-mesityl-3-pyridyl)carbamate

[0542] A solution of tert-butyl N-(4-iodo-3-pyridyl)carbamate (20.0 g,62 mmol), mesitylboric acid (10.2 g, 62 mmol), Pd(PPh₃)₄ (3.6 g, 3.12mmol), barium hydroxide octahydrate (49.3 g, 47.3 mmol) in1,2-dimethoxyethane (400 mL) and water (67 mL) was heated under refluxfor six hours. The mixture was filtered through Celite, and the filtratewas diluted with ethyl acetate, washed with brine, dried over magnesiumsulfate and evaporated, to give the title compound (containing 22.3 g ofimpurities) as pale brown crystals.

[0543]¹H NMR (400 MHz, CDCl₃) δ1.46 (s, 9H), 1.95 (s, 6H), 2.36 (s, 3H),5.95 (br s, 1H), 6.97 (d, J=4.8 Hz, 1H), 7.00 (s, 2H), 8.35 (d, J=4.8Hz, 1H), 9.42 (s, 1H).

Reference Example 72 4-Mesityl-3-pyridinamine

[0544] A 4N hydrochloric acid solution in ethyl acetate (100 mL) wasadded to a solution of tert-butyl N-(4-mesityl-3-pyridyl)carbamate (19.5g, 62 mmol) in ethyl acetate (100 mL) followed by stirring for one hour.The solution was neutralized with a 5N aqueous solution of sodiumhydroxide, extracted with ethyl acetate. The organic layer was washedwith brine, dried over anhydrous magnesium sulfate and evaporated. Theresidue was purified by silica gel column chromatography (20% ethylacetate/hexane), to give the title compound (500 mg) as white crystals.

[0545]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.33 (s, 3H), 3.53 (br s,2H), 6.88 (d, J=4.8 Hz, 1H), 6.97 (s, 2H), 8.06 (d, J=4.8 Hz, 1H), 8.19(s, 1H).

Reference Example 733-1-[(4-Mesityl-3-pyridyl)amino]ethylidenetetrahydro-2-furanone

[0546] p-Toluenesulfonic acid monohydrate (0.2 g, 1.18 mmol) was addedto a solution of 4-mesityl-3-pyridinamine (5.0 g, 24 mmol) andα-acetyl-γ-butyrolactone (6.0 g, 47 mmol) in toluene (100 mL), followedby heating under reflux for three days while removing water using aDean-Stark apparatus. The mixture was evaporated, and the resultingcrystals were washed with 60% diethyl ether/ethyl acetate, to give thetitle compound (6.0 g) as white crystals.

[0547]¹H NMR (400 MHz, CDCl₃) δ1.97 (s, 6H), 2.08 (s, 3H), 2.31 (s, 3H),2.83 (t, J=8.0 Hz, 2H), 4.27 (t, J=8.0 Hz, 2H), 6.97 (s, 2H), 7.12 (d,J=4.8 Hz, 1H), 8.40 (d, J=4.8 Hz, 1H), 8.47 (s, 1H), 9.44 (s, 1H).

Reference Example 744-Chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine

[0548] A solution of3-1-[(4-mesityl-3-pyridyl)amino]ethylidenetetrahydro-2-furanone (2.0 g,6.20 mmol), phosphorus oxychloride (5.8 mL, 6.2 mmol),N,N-dimethylaniline (98 mL, 0.78 mmol) and triethylmethylammoniumchloride (0.94 g, 6.20 mmol) in acetonitrile (10 mL) was heated underreflux for 24 hours. After cooling to room temperature, the solution wasslowly added dropwise into ice-water while stirring vigorously. Themixture was stirred for one hour while raising a temperature to roomtemperature. The mixture was diluted with ethyl acetate, and the organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(10% ethyl acetate/hexane), to give the title compound (500 mg) as whitecrystals.

[0549]¹H NMR (400 MHz, CDCl₃) δ1.87 (s, 6H), 2.39 (s, 3H), 2.71 (s, 3H),3.52 (t, J=7.6 Hz, 2H), 3.82 (t, J=7.6 Hz, 2H), 6.99 (s, 2H), 7.45 (d,J=4.4 Hz, 1H), 9.04 (d, J=4.4 Hz, 1H).

Reference Example 751-(1-Ethylpropyl)-6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,5]naphthyridine

[0550] A solution of4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine (150 mg,0.42 mmol) in 3-aminopentane (7.5 mL) was stirred at 200° C. for fourhours in a sealed tube. After evaporating, the residue was purified bysilica gel column chromatography (30-50% ethyl acetate/hexane), to givethe title compound (50 mg) as white crystals.

[0551]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 6H), 1.55-1.70 (m,4H), 1.92 (s, 6H), 2.32 (s, 3H), 2.36 (s, 3H), 3.08 (t, J=9.6 Hz, 2H),3.72 (t, J=9.6 Hz, 2H), 5.86-5.98 (m, 1H), 6.97 (s, 2H), 7.14 (d, J=4.0Hz, 1H), 8.58 (d, J=4.0 Hz, 1H).

Reference Example 76 1-Mesityl-2-methyl-3-nitrobenzene

[0552] A solution of 2-bromo-6-nitrotoluene (10.0 g, 46 mmol),mesitylboric acid (8.3 g, 51 mmol), Pd(PPh₃)₄ (2.7 g, 2.31 mmol) andbarium hydroxide octahydrate (21.9 g, 69 mmol) in 2,2-dimethoxyethane(300 mL) and water (50 mL) was heated under reflux for six hours. Themixture was filtered through Celite, and the filtrate was diluted withethyl acetate, washed with brine, dried over anhydrous magnesium sulfateand evaporated. The residue was purified by silica gel columnchromatography (0-1% ethyl acetate/hexane), to give the title compound(11.0 g) as white crystals.

[0553]¹H NMR (400 MHz, CDCl₃) δ1.90 (s, 6H), 2.15 (s, 3H), 2.34 (s, 3H),6.96 (s, 2H), 7.28 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H),7.84 (dd, J=7.6 Hz, 1.2 Hz, 1H).

Reference Example 77 3-Mesityl-2-methylaniline

[0554] Palladium-carbon (10%, 1.1 g) was added to a solution of1-mesityl-2-methyl-3-nitrobenzene (11.0 g, 43 mmol) in ethanol (220 mL)at room temperature, followed by stirring for one day in hydrogenatmosphere. The mixture was filtered through Celite and evaporated. Theresidue was purified by silica gel column chromatography (10% ethylacetate/hexane), to give the title compound (8.2 g) as white crystals.

[0555]¹H NMR (400 MHz, CDCl₃) δ1.80 (s, 3H), 1.94 (s, 6H), 2.33 (s, 3H),3.60-3.75 (br s, 2H), 6.49 (d, J=7.6 Hz, 1H), 6.69 (d, J=7.6 Hz, 1H),6.93 (s, 2H), 7.08 (t, J=7.6 Hz, 1H).

Reference Example 783-[1-(3-Mesityl-2-methylanilino)ethylidene]tetrahydro-2-furanone

[0556] A solution of 3-mesityl-2-methylaniline (5.0 g, 22 mmol) andα-acetyl-γ-butyrolactone (14.2 g, 0.11 mol) in ethanol (100 mL) washeated at reflux for three days. The mixture was evaporated, and theresidue was purified by silica gel column chromatography (10% ethylacetate/hexane), to give the title compound (7.08 g) as white crystals.

[0557]¹H NMR (400 MHz, CDCl₃) δ1.88 (s, 3H), 1.90 (s, 9H), 2.33 (s, 3H),2.92 (t, J=8.0 Hz, 2H), 4.36 (t, J=8.0 Hz, 2H), 6.91 (dd, J=7.6 Hz, 1.2Hz, 1H), 6.94 (s, 2H), 7.04 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.22 (t, J=7.6Hz, 1H), 9.80 (s, 1H).

Reference Example 794-Chloro-3-(2-chloroethyl)-7-mesityl-2,8-dimetylquinoline

[0558] A solution of3-[1-(3-mesityl-2-methylanilino)ethylidene]tetrahydro-2-furanone (2.0 g,5.96 mmol) in phosphorus oxychloride (5.6 mL) was stirred at 120° C. fortwo hours. After cooling to room temperature, the mixture was slowlyadded dropwise into ice-water while stirring vigorously, and the mixturewas stirred for one hour while raising a temperature gradually to roomtemperature. The mixture was diluted with ethyl acetate, and the organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(0-5% ethyl acetate/hexane), to give the title compound (210 mg) aswhite crystals.

[0559]¹H NMR (400 MHz, CDCl₃) δ1.90 (s, 6H), 2.36 (s, 3H), 2.47 (s, 3H),2.90 (s, 3H), 3.52 (t, J=8.0 Hz, 2H), 3.79 (t, J=8.0 Hz, 2H), 6.98 (s,2H), 7.29 (d, J=8.4 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H).

Reference Example 803-[1-(3-Iodoanilino)ethylidene]tetrahydro-2-furanone

[0560] A solution of 3-iodoaniline (5.0 g, 23 mmol),α-acetyl-γ-butyrolactone (14.6 g, 0.11 mol) in ethanol (100 mL) washeated under reflux for seven days. The mixture was evaporated, and theresidue was purified by silica gel column chromatography (10% ethylacetate/hexane), to give the title compound (7.54 g) as white crystals.

[0561]¹H NMR (400 MHz, CDCl₃) δ2.03 (s, 3H), 2.90 (t, J=8.0 Hz, 2H),4.36 (t, J=8.0 Hz, 2H), 6.99-7.07 (m, 2H), 7.41-7.48 (m, 2H), 9.96 (s,1H).

Reference Example 81 4-Chloro-3-(2-chloroethyl)-7-iodo-2-methylquinoline

[0562] A solution of3-(1-(3-iodoanilino)ethylidene]tetrahydro-2-furanone (3.0 g, 9.12 mmol)in phosphorus oxychloride (8.5 mL) was heated at reflux for two hours.After cooling to room temperature, the solution was slowly addeddropwise into ice-water while stirring vigorously. The mixture wasstirred for one hour while raising a temperature gradually to roomtemperature. The mixture was diluted with ethyl acetate, and the organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(50% methylene chloride/hexane), to give the title compound (821 mg) aswhite crystals.

[0563]¹H NMR (400 MHz, CDCl₃) δ2.82 (s, 3H), 3.46 (t, J=8.0 Hz, 2H),3.76 (t, J=8.0 Hz, 2H), 7.83 (dd, J=8.8 Hz, 1.2 Hz, 1H), 7.87 (d, J=8.8Hz, 1H), 8.44 (d, J=1.2 Hz, 1H).

Reference Example 821-(1-Ethylpropyl)-iodo-4-mesityl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline

[0564] A solution of 4-chloro-3-(2-chloroethyl)-7-iodo-2-methylquinoline(300 mg, 0.82 mmol) in 3-aminopentane (10.0 mL) was stirred at 200° C.for eight hours in a sealed tube. The mixture was evaporated, and theresidue was purified by silica gel column chromatography (10-70% ethylacetate/hexane), to give the title compound (39 mg) as a pale yellowoil.

[0565]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=7.6 Hz, 6H), 1.68-1.86 (m,4H), 2.70 (s, 3H), 3.12 (t, J=9.6 Hz, 2H), 3.88 (t, J=9.6 Hz, 2H),4.33-4.82 (m, 1H), 7.66 (dd, J=9.2 Hz, 1.2 Hz, 1H), 7.76 (d, J=9.2 Hz,1H), 8.89 (d, J=1.2 Hz, 1H).

Reference Example 831-(1-Ethylpropyl)-7-iodo-4-methyl-1H-pyrrolo[3,2-c]quinoline

[0566] Activated manganese dioxide (45 mg, 0.51 mmol) was added to asolution of1-(1-ethylpropyl)-7-iodo-4-mesityl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline(39 mg, 0.10 mmol) in toluene (4.0 mL) and methylene chloride (4.0 mL),followed by heating under reflux for one day. The mixture was filteredthrough Celite and evaporated, to give the title compound (32 mg) aspale yellow crystals.

[0567]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.6 Hz, 6H), 1.90-2.12 (m,4H), 2.90 (s, 3H), 4.92-5.00 (m, 1H), 6.83 (d, J=3.2 Hz, 1H), 7.32 (d,J=3.2 Hz, 1H), 7.77 (dd, J=8.8 Hz, 1.2 Hz, 1H), 8.06 (d, J=8.8 Hz, 1H),8.61 (d, J=1.2 Hz, 1H).

Example 18-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0568] A solution of7-chloro-6-(2-chloroethyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine(1.5 g, 4.14 mmol) and 3-aminopentane (3 mL) in methyl ethyl ketone (15mL) was heated under reflux for one hour. 3-Aminopentane (6 mL) wasadded thereto, followed by heating under reflux for further 4.5 hours.Water was added to the reaction mixture, followed by extcarting withethyl acetate, The organic layer was washed with brine, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (10-50% ethyl acetate/hexane), to givethe title compound (1.02 g) as a pale yellow oil.

[0569]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=4.8 Hz, 6H), 1.54-1.70 (m,4H), 2.02 (s, 6H), 2.16 (s, 3H), 2.27 (s, 3H), 2.31 (s, 3H), 3.08 (t,J=7.8 Hz, 2H), 3.68 (t, J=7.8 Hz, 2H), 5.60-5.69 (m, 1H), 6.94 (s, 2H).

[0570] The above-mentioned8-(1-ethylpropyl)-3-mesityl-2,5-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(1.02 g, 2.71 mmol) was dissolved in ether, and a 1 molar solution ofhydrogen chloride in ether (2.71 mL) was added slowly. The resultingcrystals were collected by filtration, washed with ether and dried, togive the title compound (1.09 g) as white crystals.

[0571]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.6 Hz, 6H), 1.64 (dq, J=6.0,7.6 Hz, 4H), 2.02 (s, 6H), 2.16 (s, 3H), 2.27 (s, 3H), 2.31 (s, 3H),3.08 (t, J=9.2 Hz, 2H), 3.67 (t, J=9.2 Hz, 2H), 5.64 (quint, 6.0 Hz 1H),6.93 (s, 2H).

[0572] MS (ESI) m/z 377 MH⁺

[0573] According to the method described in the above Example 1,compounds of Examples 2 to 65 were synthesized.

Example 28-Butyl-3-mesityl-2,5-dimethyl-7,8-dihydro-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0574] White Crystals

[0575]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.2 Hz, 3H), 1.38 (tq, J=7.2,8.0 Hz, 2H), 1.75 (tt, J=8.0, 7.2 Hz, 2H), 1.93 (s, 6H), 2.07 (s, 3H),2.25 (s, 3H), 2.29 (s, 3H), 3.10 (t, J=8.8 Hz, 2H), 4.10 (t, J=8.8 Hz,2H), 4.29 (t, J=7.2 Hz, 2H), 7.01 (s, 2H).

[0576] MS (ESI) m/z 363 MH⁺

Example 3N-5-[2,5-Dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-4-methyl-2-pyridyl-N,N-dimethylaminehydrochloride

[0577] White Crystals

[0578]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=6.8 Hz; 6H), 1.20-1.70 (m,8H), 2.25 (s, 3H), 2.37 (s, 3H), 2.61 (s, 3H), 3.17 (br s, 2H), 3.40 (s,6H), 3.95 (t, J=9.6 Hz, 2H), 5.91-6.01 (m, 1H), 6.78 (s, 1H), 8.00 (s,1H).

Example 4N-5-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-4-methyl-2-pyridyl-N,N-dimethylaminehydrochloride

[0579] White Crystals

[0580]¹H NMR (400 MHz, CDCl₃) δ0.89-1.05 (m, 6H), 1.50-1.85 (m, 4H),2.26 (s, 3H), 2.37 (s, 3H), 2.61 (s, 3H), 3.12-3.25 (m, 2H), 3.40 (s,6H), 3.94 (t, J=7.6 Hz, 2H), 5.71-5.85 (m, 1H), 6.78 (s, 1H), 7.99 (s,1H).

Example 58-Cyclopentyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0581] Grayish White Amorphous

[0582]¹H NMR (400 MHz, CDCl₃) δ1.65-1.82 (m, 6H), 1.92-2.06 (m, 2H),2.18 (s, 3H), 2.26 (s, 3H), 2.31 (s, 3H), 3.06 (t, J=9.2 Hz, 2H), 3.78(t, J=9.2 Hz, 2H), 6.04-6.15 (m, 1H), 6.94 (s, 2H).

[0583] MS (ESI) m/z 375 MH⁺

Example 63-Mesitly-2,5-dimethly-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0584] Brown Crystals

[0585]¹H NMR (400 MHz, DMSO-D₆) δ0.88 (t, J=7.2 Hz, 6H), 1.22-1.36 (m,4H), 1.54-1.64 (m, 2H), 1.64-1.76 (m, 2H), 1.93 (s, 6H), 2.07 (s, 3H),2.27 (s, 3H), 2.29 (s, 3H), 3.12 (t, J=8.4 Hz, 2H), 3.99 (t, J=8.4 Hz,2H), 5.82-5.90 (m, 1H), 7.01 (s, 2H), 12.79 (br s, 1H).

[0586] MS (ESI) m/z 405 MH⁺

Example 74-[2-(3-Mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethyl]morpholine

[0587] Yellow Oil

[0588]¹H NMR (400 MHz, CDCl₃) δ2.01 (s, 6H), 2.15 (s, 3H), 2.28 (s, 3H),2.31 (s, 3H), 2.59 (br s, 4H), 2.73 (t, J=6.4 Hz, 2H), 3.10 (t, J=9.2Hz, 2H), 3.64 (t, J=4.4 Hz, 4H), 3.85 (J=9.2 Hz, 2H), 4.36 (t, J=6.4 Hz,2H), 6.94 (s, 2H).

Example 88-(1-Ethylpropyl)-2,5-dimethyl-3-(3-methyl-2-naphthyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0589] White Crystals

[0590]¹H NMR (400 MHz, CDCl₃) δ0.93-1.10 (m, 6H), 1.55-1.87 (m, 4H),2.24 (s, 3H), 2.36 (s, 3H), 2.67 (s, 3H), 3.10-3.27 (m, 2H), 3.87-4.05(m, 2H), 5.88 (br s, 1H), 7.33-7.48 (m, 2H), 7.70 (s, 1H), 7.73-7.83 (m,3H).

Example 92,5-Dimethyl-3-(3-methyl-2-naphthyl)-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0591] White Crystals

[0592]¹H NMR (400 MHz, CDCl₃); δ (ppm) 0.93-1.05 (m, 6H), 1.23-1.78 (m,8H), 2.24 (s, 3H), 2.36 (s, 3H), 2.66 (s, 3H), 3.10-3.23 (m, 2H),3.90-4.00 (m, 2H), 6.00-6.10 (m, 1H), 7.35-7.48 (m, 2H), 7.70 (s, 1H),7.73-7.83 (m, 3H).

Example 103-Mesityl-2,5-dimethyl-8-(2,2,6,6-tetramethyl-4-pipyridyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0593] White Crystals

[0594]¹H NMR (400 MHz, CDCl₃) δ1.21 (S, 6H), 1.42 (s, 6H), 1.40-1.60 (m,2H), 1.85 (dd, J=12.0, 2.8 Hz, 2H), 2.03 (s, 6H), 2.15 (s, 3H), 2.27 (s,3H), 2.31 (s, 3H), 3.05 (t, J=9.2 Hz, 2H), 3.75 (t, J=9.2 Hz, 2H), 6.20(tt, J=12.0, 2.8 Hz, 1H), 6.94 (s, 2H).

[0595] MS (ESI) m/z 446 MH⁺

Example 118-Isopropyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0596] Grayish White Solid

[0597]¹H NMR (400 MHz, CDCl₃) δ1.36 (d, J=6.8 Hz, 6H), 1.93 (s, 6H),2.07 (s, 3H), 2.26 (s, 3H), 2.29 (s, 3H), 3.08 (t, J=8.4 Hz, 2H), 4.08(t, J=8.4 Hz, 2H), 5.93 (hept., J=6.8 Hz, 1H), 7.00 (s, 2H), 12.69 (s,1H).

[0598] MS (ESI) m/z 349 MH⁺

Example 12 9-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[0599] White Amorphous

[0600]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.60-1.73 (m,4H), 1.96-2.05 (m, 2H), 2.03 (s, 6H), 2.18 (s, 3H), 2.31 (s, 3H), 2.33(s, 3H), 2.68 (t, J=6.4 Hz, 2H), 3.32 (t, J=5.6 Hz, 2H), 6.04-6.12 (m,1H), 6.94 (s, 2H).

Example 138-(1-Ethylpropyl)-3-mesityl-2,5,7-trimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0601] White Crystals

[0602]¹H NMR (400 MHz, CDCl₃) δ0.82 (t, J=6.8 Hz, 3H), 1.13 (t, J=6.8Hz, 3H), 1.39 (d, J=5.6 Hz, 3H), 1.60-1.90 (m, 4H), 2.03 (s, 6H), 2.17(s, 3H), 2.27 (s, 3H), 2.31 (s, 3H), 2.52-2.62 (m, 1H), 3.34-3.62 (m,1H), 4.07-4.22 (m, 1H), 5.45 (br s, 1H), 6.93 (s, 2H).

Example 143-(4-Bromophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0603] White Crystals

[0604]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.5 Hz, 6H), 1.50-1.75 (m,4H), 2.35 (s, 3H), 2.52 (s, 3H), 3.10 (t, J=9.2 Hz, 2H), 3.68 (t, J=9.2Hz, 2H), 5.55-5.70 (m, 1H), 7.52 (d, J=8.6 Hz, 2H), 7.66 (d, J=8.6 Hz,2H).

[0605] MS (ESI) m/z 415 MH⁺

Example 153-(4-Bromophenyl)-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0606] White Crystals

[0607]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.4 Hz, 3H), 1.58-1.78 (m,2H), 2.35 (s, 3H), 2.51 (s, 3H), 3.09 (dd, J=3.7, 8.4 Hz, 2H), 3.34 (s,3H), 3.51 (dd, J=4.3, 10.4 Hz, 1H), 3.62 (dd, J=7.6, 10.4 Hz, 1H),3.69-3.91 (m, 2H), 5.88-6.04 (m, 1H), 7.51 (d, J=8.4 Hz, 2H), 7.65 (d,J=8.4 Hz, 2H).

Example 163-(4-Bromophenyl)-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0608] White Crystals

[0609]¹H NMR (400 MHz, CDCl₃) δ0.92 (t, J=7.3 Hz, 6H), 1.22-1.44 (m,4H), 1.45-1.65 (m, 4H), 2.35 (s, 3H), 2.51 (s, 3H), 3.09 (t, J=9.2 Hz,2H), 3.68 (t, J=9.2 Hz, 2H), 5.80-5.91 (m, 1H), 7.51 (d, J=8.6 Hz, 2H),7.66 (d, J=8.6 Hz, 2H).

Example 178-(1-Ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethoxyphenyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0610] Pale Yellow Crystals

[0611]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.4 Hz, 6H), 1.50-1.73 (m,4H), 2.22 (s, 3H), 2.30 (s, 3H), 3.05 (t, J=9.0 Hz, 2H), 3.66 (t, J=9.0Hz, 2H), 3,74 (s, 6H), 3.85 (s, 3H), 5.60-5.73 (m, 1H), 6.24 (s, 2H).

Example 188-[1-(Methoxymethyl)propyl]-2,5-dimethyl-3-(2,4,6-trimethoxyphenyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0612] Pale Yellow Crystals

[0613]¹H NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.4 Hz, 3H), 1.60-1.75 (m,2H), 2.21 (s, 3H), 2.28 (s, 3H), 3.03 (dd, J=3.0, 7.2 Hz, 1H), 3.06 (dd,J=3.0, 7.2 Hz, 1H), 3.36 (s, 3H), 3.55 (dd, J=4.4, 10.4 Hz, 1H), 3.64(dd, J=6.7, 10.4 Hz, 1H), 3.68-3.88 (m, 2H), 3.72 (s, 3H), 3.73 (s, 3H),3.85 (s, 3H), 5.85-6.00 (m, 1H), 6.24 (s, 2H).

Example 192,5-Dimethyl-8-(1-propylbutyl)-3-(2,4,6-trimethoxyphenyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0614] Yellow Crystals

[0615]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.3 Hz, 6H), 1.26-1.64 (m,8H), 2.21 (s, 3H), 2.27 (s, 3H), 3.03 (t, J=9.1 Hz, 2H), 3.64 (t, J=9.1Hz, 2H), 3.73 (s, 6H), 3.85 (s, 3H), 5.80-5.92 (m, 1H), 6.24 (s, 2H).

Example 203-(1,3-Benzodioxol-5-yl)-yl-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0616] Pale Yellow Crystals

[0617]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.4 Hz, 6H), 1.50-1.71 (m,4H), 2.34 (s, 3H), 2.50 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.67 (t, J=9.2Hz, 2H), 5.58-5.73 (m, 1H), 5.96 (s, 2H), 6.87 (d, J=8.1 Hz, 1H), 7.14(dd, J=1.6, 8.1 Hz, 1H), 7.31 (d, J=1.5 Hz, 1H).

Example 213-(1,3-Benzodioxol-5-yl)-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0618] Pale Yellow Crystals

[0619]¹H NMR (400 MHz, CDCl₃); δ (ppm) 0.92 (t, J=7.3 Hz, 6H), 1.24-1.44(m, 4H), 1.45-1.68 (m, 4H), 2.34 (s, 3H), 2.49 (s, 3H), 3.08 (t, J=9.2Hz, 2H), 3.67 (t, J=9.2 Hz, 2H), 5.80-5.94 (m, 1H), 5.95 (s, 2H), 6.86(d, J=8.1 Hz, 1H), 7.14 (dd, J=1.7, 8.1 Hz, 1H), 7.32 (d, J=1.7 Hz, 1H).

Example 228-(1-Ethylpropyl)-2,5-dimethyl-3-phenyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0620] Pale Yellow Crystal

[0621]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.4 Hz, 6H), 1.50-1.66 (m,4H), 2.35 (s, 3H), 2.54 (s, 3H), 3.10 (t, J=9.1 Hz, 2H), 3.68 (t, J=9.1Hz, 2H), 5.60-5.74 (m, 1H), 7.20 (t, J=7.4 Hz, 1H), 7.41 (t, J=7.8 Hz,2H), 7.76 (dd, J=1.2, 8.3 Hz, 2H).

Example 232-Ethyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0622] Pale Yellow Crystals

[0623]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.4 Hz, 6H), 1.15 (t, J=7.5Hz, 3H), 1.53-1.72 (m, 4H), 2.02 (s, 6H), 2.27 (s, 3H), 2.30 (s, 3H),2.51 (q, J=7.5 Hz, 2H), 3.08 (t, J=9.1 Hz, 2H), 3.67 (t, J=9.1 Hz, 2H),5.60-5.75 (m, 1H), 6.92 (s, 2H).

Example 248-(tert-Butyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0624] Brown Crystals

[0625]¹H NMR (400 MHz, CDCl₃) δ1.83 (s, 9H), 2.03 (s, 6H), 2.18 (s, 3H),2.32 (s, 3H), 2.63 (s, 3H), 3.07 (t, J=7.9 Hz, 2H), 4.27 (t, J=7.9 Hz,2H), 6.98 (s, 2H).

[0626] MS (ESI) m/z 363 MH⁺

Example 253-Mesityl-2,5,8-trimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0627] White Crystals

[0628]¹H NMR (400 MHz, CDCl₃) δ1.66 (s, 3H), 2.02 (s, 6H), 2.19 (s, 3H),2.28 (s, 3H), 2.31 (s, 3H), 3.08 (t, J=9.2 Hz, 2H), 3.73 (t, J=9.2 Hz,2H), 6.94 (s, 2H).

[0629] MS (ESI) m/z 321 MH⁺

Example 268-Benzyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0630] Brown Crystals

[0631]¹H NMR (400 MHz, CDCl₃); δ (ppm) 2.05 (s, 6H), 2.20 (s, 3H), 2.33(s, 3H), 2.68 (s, 3H), 3.14 (t, J=9.0 Hz, 2H), 3.95 (t, J=9.0 Hz, 2H),5.65 (s, 2H), 7.00 (s, 2H), 7.32-7.47 (m, 5H).

[0632] MS (ESI) m/z 397 MH⁺

Example 273-Mesityl-8-(2-methoxyethyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0633] Brown Crystals

[0634]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.14 (s, 3H), 2.32 (s, 3H),2.66 (s, 3H), 3.18 (t, J=9.2 Hz, 2H), 3.42 (s, 3H), 3.82 (t, J=4.8 Hz,2H), 4.23 (t, J=9.2 Hz, 2H), 4.55 (t, J=4.8 Hz, 2H), 6.97 (s, 2H).

[0635] MS (ESI) m/z 365 MH⁺

Example 283-Mesityl-2,5-dimethyl-8-propyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0636] Brown Crystals

[0637]¹H NMR (400 MHz, CDCl₃) δ1.06 (t, J=7.2 Hz, 3H), 1.88 (tq, J=7.2,7.2 Hz, 2H), 2.01 (s, 6H), 2.16 (s, 3H), 2.32 (s, 3H), 2.62 (s, 3H),3.21 (t, J=5.7Hz, 2H), 4.13 (t, J=5.7 Hz, 2H), 4.34 (t, J=7.2 Hz, 2H),6.97 (s, 2H).

[0638] MS (ESI) m/z 349 MH⁺

Example 298-(1-Ethylpropyl)-2-cyclopropyl-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidineExample 304-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]benzonitrile

[0639] Pale Yellow Crystals

[0640]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.4 Hz, 6H), 1.51-1.73 (m,4H), 2.37 (s, 3H), 2.58 (s, 3H), 3.12 (t, J=9.2 Hz, 2H), 3.70 (t, J=92Hz, 2H), 5.55-5.71 (m, 1H), 7.66 (dd, J=1.8, 6.8 Hz, 2H), 7.99 (dd,J=1.8, 6.8 Hz, 2H).

[0641] MS (ESI) m/z 360 MH⁺

Example 314-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]benzamide

[0642] White Crystals

[0643]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.3 Hz, 6H), 1.50-1.75 (m,4H), 2.37 (s, 3H), 2.57 (s, 3H), 3.11 (t, J=9.2 Hz, 2H), 3.69 (t, J=9.2Hz, 2H), 5.60-5.73 (m, 1H), 7.85 (d, J=8.6 Hz, 2H), 7.92 (d, J=8.6 Hz,2H).

[0644] MS (ESI) m/z 378 MH⁺

Example 328-(1-Ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0645] Pink Crystals

[0646]¹H NMR (400 MHz, CDCl₃) δ1.13 (t, J=7.3 Hz, 6H), 1.77-2.00 (m,4H), 2.25 (s, 6H), 2.47 (s, 3H), 2.87 (s, 3H), 3.30-3.40 (m, 2H),4.07-4.18 (m, 2H), 5.90-6.04 (m, 1H), 7.13 (s, 2H), 8.03 (s, 1H).

Example 33 3-(2,4-Dichlorophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine hydrochloride

[0647] Yellow Crystals

[0648]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=6.4 Hz, 3H), 1.00 (t, J=6.8Hz, 3H), 1.55-1.82 (m, 4H), 2.28 (s, 3H), 2.69 (s, 3H), 3.10-3.22 (m,2H), 3.87-4.00 (m, 2H), 5.74-5.87 (m, 1H), 7.40 (s, 2H), 7.53 (s, 1H).

Example 343-(2,4-Dichlorophenyl)-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0649] White Crystals

[0650]¹H NMR (400 MHz, CDCl₃) δ0.92-1.01 (m, 6H), 1.18-1.72 (m, 8H),2.27 (s, 3H), 2.67 (s, 3H), 3.15 (t, J=8.8 Hz, 2H), 3.94 (t, J=9.2 Hz,2H), 6.00 (quint, 6.0 Hz, 1H), 7.40 (s, 2H), 7.53 (s, 1H).

Example 353-Mesityl-2,5-dimethyl-8-nonyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrocloride

[0651] Brown Oil

[0652]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.2 Hz, 3H), 1.15-1.52 (m,12H), 1.70-1.90 (m, 2H), 2.02 (s, 6H), 2.16 (s, 3H), 2.33 (s, 3H), 2.67(s, 3H), 3.16 (br s, 2H), 4.09 (br s, 2H), 4.36 (t, J=7.2 Hz, 2H), 6.98(s, 2H).

[0653] MS (ESI) m/z 433MH⁺

Example 368-Cyclopropyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0654] Pale Brown Crystals

[0655]¹H NMR (400 MHz, CDCl₃) δ1.04-1.14 (m, 4H), 2.03 (s, 6H), 2.17 (s,3H), 2.33 (s, 3H), 2.63 (s, 3H), 3.10 (t, J=8.9 Hz, 2H), 3.94 (t, J=9.2Hz, 2H), 4.00-4.10 (m, 1H), 6.98 (s, 2H).

[0656] MS (ESI) m/z 347 MH⁺

Example 378-Ethyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimdinehydrochloride

[0657] Brown Solid

[0658]¹H NMR (400 MHz, CDCl₃) δ1.47 (t, J=7.2 Hz, 3H), 2.02 (s, 6H),2.16 (s, 3H), 2.33 (s, 3H), 2.67 (s, 3H), 3.19 (t, J=8.8 Hz, 2H), 4. 11(t, J=8.8 Hz, 2H), 4.45 (q, J=7.2 Hz, 2H), 6.98 (s, 2H).

[0659] MS (ESI) m/z 335MH⁺

Example 388-(Cyclopropylmethyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0660] Brown Crystals

[0661]¹H NMR (400 MHz, CDCl₃) δ0.46 (dd, J=10.3, 3.8 Hz, 2H), 0.72 (dd,J=11.0, 3.8 Hz, 2H), 1.18-1.26 (m, 1H), 2.03 (s, 6H), 2.16 (s, 3H), 2.33(s, 3H), 2.69 (s, 3H), 3.21 (t, J=8.4 Hz, 2H), 4.22 (t, J=8.4 Hz, 2H),4.32 (d, J=7.2 Hz, 2H), 6.99 (s, 2H).

[0662] MS (ESI) m/z 361 MH⁺

Example 393-Mesityl-8-(3-methoxypropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0663] Brown Crystals

[0664]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.08 (tt, J=7.2, 5.6 Hz,2H), 2.16 (s, 3H), 2.32 (s, 3H), 2.52 (s, 3H), 3.13 (t, J=8.8 Hz, 2H),3.27 (s, 3H), 3.55 (t, J=5.6 Hz, 2H), 3.99 (t, J=8.8 Hz, 2H), 4.39 (t,J=7.2 Hz, 2H), 6.96 (s, 2H).

[0665] MS (ESI) m/z 379 MH⁺

Example 403-Mesityl-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0666] Brown Crystals

[0667]¹H NMR (400 MHz, CDCl₃) δ1.05 (t, J=6.9 Hz, 3H), 1.68-1.84 (m,2H), 2.02 (s, 3H), 2.04 (s, 3H), 2.16 (s, 3H), 2.33 (s, 3H), 2.69 (s,3H), 3.10-3.22 (m, 2H), 3.38 (s, 3H), 3.62-3.68 (m, 2H), 3.80-4.40 (m,4H), 6.06-6.14 (m, 1H), 6.98 (m, 2H).

[0668] MS (ESI) m/z 393 MH⁺

Example 413-(2-Chlorophenyl)-8-(1-ethylproptyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0669] White Amorphous

[0670]¹H NMR (400MHz, CDCl₃) δ0.95 (t, J=7.2 Hz, 6H), 1.55-1.72 (m, 4H),2.30 (s, 3H), 2.32 (s, 3H), 3.09 (t, J=8.8 Hz, 2H), 3.68 (t, J=8.8 Hz,2H), 5.68 (br s, 1H), 7.23 (ddd, J=1.6, 7.6, 7.6 Hz, 1H), 7.29 (ddd,J=1.6, 7.2, 7.6 Hz, 1H), 7.43 (dd, J=2.0, 7.6 Hz, 1H), 7.47 (dd, J=1.2,7.6 Hz, 1H).

Example 423-(2-Chlorophenyl)-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0671] Yellow Amorphous

[0672]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.2 Hz, 6H), 1.28-1.45(m, 4H),1.46-1.66 (m, 4H), 2.30 (s, 3H), 2.31 (s, 3H), 3.08 (t, J=8.8 Hz, 2H),3.69 (t, J=8.8 Hz, 2H), 5.86 (br s, 1H), 7.23 (ddd, J=1.2, 7.2, 8.0 Hz,1H), 7.29 (ddd, J=1.2, 7.2, 7.6 Hz, 1H), 7.43 (dd, J=2.0, 7.6 Hz, 1H),7.47 (dd, J=1.6, 8.0 Hz, 2H).

Example 438-Butyl-3-mesityl-2,5,7-trimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0673] Pale Yellow Crystals

[0674]¹H NMR (400 MHz, DMSO-d₆) δ0.94 (t, J=6.8 Hz, 3H), 1.32-1.43 (m,2H), 1.42 (d, J=6.0 Hz, 3H), 1.62-1.74 (m, 1H), 1.75-1.86 (m, 1H), 1.93(s, 6H), 2.06 (s, 3H), 2.26 (s, 3H), 2.29 (s, 3H), 2.65-2.76 (m, 1H),3.28-3.40 (m, 1H), 3.73-3.83 (m, 1H), 4.52 (br s, 1H), 4.66-4.80 (m,1H), 7.00 (s, 2H).

Example 443-Mesityl-8-(2-methoxyethyl)-2,5,7-trimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0675] Pale Yellow Crystals

[0676]¹H NMR (400 MHz, DMSO-d₆) δ1.42 (d, J=6.4 Hz, 3H), 1.929 (s, 3H),1.933 (s, 3H), 2.07 (s, 3H), 2.27 (s, 3H), 2.29 (s, 3H), 2.72 (dd, J=4.8Hz, 16.4, 1H), 3.28 (s, 3H), 3.35 (dd, J=10.4, 15.6 Hz, 1H), 3.63-3.79(m, 2H), 3.83-3.92 (m, 1H), 4.50-4.60 (m, 1H), 5.10-5.20 (m, 1H), 7.00(s, 2H), 12.84 (br s, 1H).

Example 458-Cycloheptyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0677] Pale Brown Crystals

[0678]¹H NMR (400 MHz, CDCl₃) δ1.54-1.89 (m, 10H), 2.03 (s, 6H),2.04-2.14 (m, 2H), 2.17 (s, 3H), 2.33 (s, 3H), 2.65 (s, 3H), 3.13 (t,J=8.8 Hz, 2H), 4.07 (t, J=8.8 Hz, 2H), 5.86-5.92 (m, 1H), 6.98 (s, 2H).

[0679] MS (ESI) m/z 403 MH⁺

Example 463-Mesityl-2,5-dimethyl-8-(2-pyridylmethyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0680] Pale Brown Crystals

[0681]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.15 (s, 3H), 2.32 (s, 3H),2.69 (s, 3H), 3.20 (t, J=8.8 Hz, 2H), 4.19 (t, J=8.8 Hz, 2H), 5.84 (s,2H), 6.98 (s, 2H), 7.40 (t, J=6.0 Hz, 1H), 7.56-7.66 (m, 1H), 7.89 (t,J=6.0 Hz, 1H), 8.63 (d, J=3.6 Hz, 1H).

[0682] MS (ESI) mn/z 398 MH⁺

Example 478-Cyclohexyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0683] Brown Crystals

[0684]¹H NMR (400 MHz, CDCl₃) δ1.46-1.68 (m, 4H), 1.74-2.10 (m, 6H),2.03 (s, 6H), 2.16 (s, 3H), 2.33 (s, 3H), 2.65 (s, 3H), 3.14 (t, J=8.8Hz, 2H), 4.07 (t, J=8.8 Hz, 2H), 5.61-5.72 (m, 1H), 6.98 (s, 2H).

[0685] MS (ESI) m/z 389 MH⁺

Example 483-Mesityl-2,5-dimethyl-8-(2-methylcyclohexyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0686] Gray Crystals

[0687]¹H NMR (400 MHz, CDCl₃) δ0.95-1.14 (d×2, J=7.2, 6.4 Hz, 3H),1.23-2.00, 2.55-2.63 (m, 9H), 2.00-2.09 (s×3, 6H), 2.13-2.20 (s×2, 3H),2.33 (s, 3H), 2.63-2.69 (s×2, 3H), 3.08-3.20 (m, 2H), 3.93-4.18 (m, 2H),5.49-5.58 (m, 1H), 6.98 (s, 2H).

[0688] MS (ESI) m/z 403 MH⁺

Example 493-(2,4-Dimethoxyphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0689] Brown Oil

[0690]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.2 Hz, 3H), 2.51-2.70 (m,4H), 2.29 (s, 3H), 2.30 (s, 3H), 3.07 (t, J=8.8 Hz, 2H), 3.66 (t, J=9.6Hz, 2H), 3,78 (s, 3H), 3.84 (s, 3H), 5.65 (br s, 1H), 6.56 (d, J=2.8 Hz,1H), 6.59 (dd, J=2.8, 10.8 Hz, 1H), 7.36 (d. J=8.0 Hz, 1H).

Example 508-(1-Ethylpropyl)-2,5-dimethyl-3-(2-methylphenyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0691] White Crystals

[0692]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.6 Hz, 3H), 1.00 (t, J=7.2Hz, 3H), 1.65-1.85 (m, 4H), 2.20 (s, 3H), 2.25 (s, 3H), 2.68 (s, 3H),3.10-3.22 (m, 2H), 3.85-3.97 (m, 2H), 5.78-5.92 (m, 1H), 7.17-7.40 (m,4H).

Example 512,5-Dimethyl-3-(2-methylphenyl)-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0693] White Crystals

[0694]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=7.2 Hz, 3H), 0.98 (t, J=6.8Hz, 3H), 1.20-1.50 (m, 8H), 2.20 (s, 3H), 2.24 (s, 3H), 2.67 (s, 3H),3.15 (t, J=8.8 Hz, 2H), 3.93 (t, J=8.4 Hz, 2H), 6.03 (quint, J=6.0 Hz,1H), 7.15-7.40 (m, 4H).

Example 528-[1-(Methoxymethyl)propyl]-2,5-dimethyl-3-(2-methylphenyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0695] White Crystals

[0696]¹H NMR (400 MHz, CDCl₃) δ1.00-1.08 (m, 3H), 1.70-1.82 (m, 2H),2.19 (d, J=3.6 Hz, 3H), 2.24 (s, 3H), 2.68 (s, 3H), 3.10-3.19 (m, 2H),3.38 (d, J=3.2 Hz, 3H), 3.58-3.67 (m, 2H), 3.93-4.17 (m, 2H), 6.05-6.18(m, 1H), 7.15-7.38 (m, 4H).

Example 533-(4-Chloro-2-methoxyphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0697] Yellow Crystals

[0698]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.2 Hz, 3H), 1.50-1.70 (m,4H), 2.29 (s, 3H), 2.31 (s, 3H), 2.39 (s, 3H), 3.06 (t, J=9.6 Hz, 2H),3.65 (t, J=8.4 Hz, 2H), 3.79 (s, 3H), 5.66 (br s, 1H), 6.78 (s, 1H),6.85 (d, J=8.4 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H).

Example 543-(3-Chlorophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0699] Yellow Crystals

[0700]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.52-1.74 (m,4H), 2.36 (s, 3H), 2.54 (s, 3H), 3.10 (t, J=8.8 Hz, 2H), 3.68 (t, J=8.8Hz, 2H), 5.65 (br s, 1H), 7.16 (ddd, J=1.2, 2.0, 8.0 Hz, 1H), 7.32 (dd,J=8.0, 8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.79 (dd, J=1.6, 2.0 Hz,1H).

Example 553-(4-Chlorophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0701] Yellow Crystals

[0702]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.55-1.70 (m,4H), 2.35 (s, 3H), 2.52 (s, 3H), 3.10 (t, J=8.8 Hz, 2H), 3.68 (t, J=8.8Hz, 2H), 5.65 (br s, 1H), 7.37 (ddd, J=2.0, 2.8, 8.4 Hz, 2H), 7.72 (ddd,J=2.0, 2.4, 8.8 Hz, 2H).

Example 563-(2,6-Dimethylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0703] Yellow Crystals

[0704]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 6H), 1.56-1.72 (m,4H), 2.06 (s, 6H), 2.16 (s, 3H), 2.27 (s, 3H), 3.08 (t, J=8.8 Hz, 2H),3.68 (t, J=8.8 Hz, 2H), 5.66 (br s, 1H), 7.07-7.18 (m, 3H).

Example 573-(2,6-Dimethylphenyl)-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0705] Yellow Crystals

[0706]¹H NMR (400 MHz, DMSO-d₆) δ0.88 (t, J=6.4 Hz, 6H), 1.18-1.38 (m,4H), 1.51-1.64 (m, 2H), 1.64-1.76 (m, 2H), 1.96 (s, 6H), 2.06 (s, 3H),2.26 (s, 3H), 3.12 (br s, 2H), 3.96 (br s, 2H), 5.84 (br s, 1H),7.10-7.20 (m, 2H), 7.20-7.30 (m, 1H).

Example 58N-[2-(3-Mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine-8-yl)ethyl]-N,N-dimethylaminehydrochloride

[0707] White Crystals

[0708]¹H NMR (400 MHz, CDCl₃) δ2.03 (s, 6H), 2.15 (s, 3H), 2.31 (s, 3H),2.46 (s, 3H), 3.05 (s, 6H), 3.24 (br s, 2H), 3.74 (br s, 2H), 4.31 (brs, 2H), 4.90 (br s, 2H), 6.95 (s, 2H).

[0709] MS (ESI) m/z 378 MH⁺

Example 593-(3-Mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-propanolhydrochloride

[0710] White Crystals

[0711]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.00-2.11 (m, 2H), 2.17 (s,3H), 2.32 (s, 3H), 2.58 (s, 3H), 3.14-3.28 (m, 2H), 3.73 (t, J=5.6 Hz,2H), 4.15-4.25 (m, 2H), 4.46 (t, J=6.0 Hz, 2H), 6.97 (s, 2H).

[0712] MS (ESI) m/z 365 MH⁺

Example 603-(4-Bromo-2-methylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0713] White Crystals

[0714]¹H NMR (400 MHz, CDCl₃) δ0.88-1.02 (m, 6H), 1.52-1.74 (m, 4H),2.20 (s, 3H), 2.27 (s, 3H), 2.29 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.68(t, J=9.2 Hz, 2H), 5.58-5.70 (m, 1H), 7.12 (d, J=8.1 Hz, 1H), 7.32 (dd,J=2.0, 8.1 Hz, 1H), 7.43 (d, J=2.0 Hz, 1H).

Example 618-Butyl-3-mesityl-2,5-dimethyl-7-propyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimdinehydrochloride

[0715] Pale Yellow Crystals

[0716]¹H NMR (400 MHz, CDCl₃) δ0.95-1.12 (m, 6H), 1.36-1.56 (m, 4H),1.63-1.80 (m, 2H), 1.80-2.00 (m, 2H), 2.03 (s, 6H), 2.16 (s, 3H), 2.32(s, 3H), 2.65 (s, 3H), 2.83 (br s, 1H), 3.29 (br s, 1H), 3.69 (br s,1H), 4.35 (br s, 1H), 4.98 (br s, 1H), 6.97 (s, 2H).

Example 623-Mesityl-8-(2-methoxyethyl)-2,5-dimethyl-7-propyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pryrimidinehydrochloride

[0717] Pale Yellowish White Powder

[0718]¹H NMR (400 MHz, CDCl₃) δ1.04 (t, J=6.8 Hz, 3H), 1.34-1.50 (m,2H), 1.61-1.77 (m, 1H), 1.88-2.10 (m, 1H), 2.03 (s, 6H), 2.15 (s, 3H),2.32 (s, 3H), 2.64 (s, 3H), 2.76-2.86 (m, 1H), 3.23-3.25 (m, 1H), 3.39(s, 3H), 3.70-3.85 (m, 3H), 4.51 (br s, 1H), 5.25-5.38 (m, 1H), 6.97 (s,2H).

Example 633-Mesityl-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0719] White Crystals

[0720]¹H NMR (400 MHz, CDCl₃) δ2.01 (s, 6H), 2.14 (s, 3H), 2.26 (s, 3H),2.30 (s, 3H), 3.07 (t, J=9.2 Hz, 2H), 3.38 (s, 6H), 3.67 (dd, J=10.0,4.8 Hz, 2H), 3.78 (dd, J=10.0, 6.8 Hz, 2H), 3.92 (t, J=9.2 Hz, 2H),6.17-6.27 (m, 1H), 6.93 (s, 2H).

[0721] MS (ESI) m/z 409 MH⁺

Example 643-(2,4-Dimethylphenyl)-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidinehydrochloride

[0722] White Crystals

[0723]¹H NMR (400 MHz, CDCl₃) δ2.15 (s, 3H), 2.21 (s, 3H), 2.37 (s, 3H),2.69 (s, 3H), 3.15 (t, J=9.2 Hz, 2H), 3.40 (s, 6H), 3.66-3.74 (m, 2H),3.77-3.85 (m, 2H), 4.19 (t, J=9.2 Hz, 2H), 6.25-6.33 (m, 1H), 7.07 (s,1H), 7.08 (s, 1H), 7.16 (s, 1H).

[0724] MS (ESI) m/z 395 MH⁺

Example 653-(2,4-Dimethylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidenehydrochloride

[0725] White Crystals

[0726]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.6 Hz, 3H), 1.00 (t, J=7.6Hz, 3H), 1.70-1.90 (m, 4H), 2.16 (s, 3H), 2.24 (s, 3H), 2.37 (s, 3H),2.69 (s, 3H), 3.17 (br s, 2H), 3.94 (br s, 2H), 5.87 (br s, 1H), 7.08(s, 2H), 7.17 (s, 1H).

[0727] MS (ESI) m/z 363 MH⁺

Example 668-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimiden-7-one

[0728] Water (7 mg) was added to a solution of potassium tert-butoxide(43 mg) in tetrahydrofuran (10 mL), and a solution of ethyl2-[7-[(1-ethylpropyl)amino]-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl]acetate(84 mg) obtained in Preparation Example 30 in tetrahydrofuran (5 mL) wasadded dropwise, followed by stirring at room temperature for two hours.The reaction mixture was adjusted to about pH 5 with acetic acid,extracted twice with ethyl acetate, and then washed twice with brine.After the organic layer was dried over anhydrous magnesium sulfate, thesolvent was evaporated, to give 23 mg of carboxylic acid,(2-[7-[(1-ethylpropyl)amino]-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl]aceticacid). Methylene chloride (5 mL) was added to the carboxylic acid,1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (WSC) (12mg) and a catalytic amount of 4-dimethylaminopyridine were further addedsuccessively, followed by stirring at room temperature for one hour.After the solvent was removed, water was added thereto and the mixturewas extracted twice with ethyl acetate. The organic layer was washedtwice with brine, dried over anhydrous magnesium sulfate and the solventwas evaporated. The residue was purified by silica columnchromatography, to give the title compound (20 mg) as deep-red crystals.

[0729]¹H NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.2 Hz, 6H), 1.23-1.36 (m,2H), 1.57 (m, 2H), 2.03 (s, 6H), 2.25 (s, 3H), 2.34 (s, 3H), 2.63 (s,3H), 4.02-4.25 (m, 2H), 5.86 (m, 1H), 6.96 (s, 2H).

Example 678-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0730] A solution of8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(468 mg, 1,24 mmol) in N-methyl-2-pyrrolidinone (10 mL) was heated at200° C. for 15 hours. Water was added to the reaction solution, and themixture was extracted with ethyl acetate, washed with brine, and thendried over anhydrous magnesium sulfate. The solvent was evaporated, andthe residue was subjected to silica gel column cromatography (10% ethylacetate/hexane), to give the title compound (168 mg, 36%) as pale yellowcrystals.

[0731]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.3 Hz, 6H), 1.80-2.08 (m,4H), 2.04 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.63 (s, 3H), 5.88-6.02(m, 1H), 6.59 (d, J=3.5 Hz, 1H), 6.85 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

[0732] According to the method described in the above Example 67,compounds of Examples 68-71 were synthesized.

Example 688-(1-Ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethoxyphenyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimridine

[0733] Pale Pink Crystals

[0734]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.3 Hz, 6H), 1.76-2.04 (m,4H), 2.32 (s, 3H), 2.63 (s, 3H), 3.75 (s, 6H), 3.87 (s, 3H), 5.85-6.03(m, 1H), 6.28 (s, 2H), 6.55 (d, J=3.5 Hz, 1H), 6.81 (d, J=3.5 Hz, 1H).

Example 693-(2,4-Dichlorophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0735] White Crystals

[0736]¹H NMR (400 MHz, CDCl₃) δ0.79 (t, J=7.3 Hz, 6H), 1.70-1.99 (m,4H), 2.33 (s, 3H), 2.60 (s, 3H), 5.79-5.97 (m, 1H), 6.54 (d, J=3.5 Hz,1H), 6.81 (d, J=3.5 Hz, 1H), 7.25 (dd, J=2.2, 8.2 Hz, 1H), 7.34 (d,J=8.2 Hz, 1H), 7.46 (d, J=2.2 Hz, 1H).

Example 703-(2,4-Dichlorophenyl)-2,5-dimethyl-8-(1-propylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0737] Pale Yellow Crystals

[0738]¹H NMR (400MHz, CDCl₃) δ0.90 (t, J=7.3 Hz, 6H), 1.06-1.22 (m, 2H),1.24-1.40 (m, 2H), 1.77-1.92 (m, 4H), 2.39 (s, 3H), 2.66 (s, 3H),6.06-6.23 (m, 1H), 6.61 (d, J=3.5 Hz, 1H), 6.88 (d, J=3.5 Hz, 1H), 7.32(dd, J=2.0, 8.2 Hz, 1H), 7.41 (d, J=8.2 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H).

Example 713-(4-Bromophenyl)8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimdine

[0739] Yellow Crystals

[0740]¹H NMR (400 MHz, CDCl₃) δ0.84 (t, J=7.3 Hz, 6H), 1.76-2.06 (m,4H), 2.65 (s, 3H), 2.75 (s, 3H), 5.87-6.02 (m, 1H), 6.65 (d, J=3.5 Hz,1H), 6.91 (d, J=3.5 Hz, 1H), 7.72 (d, J=8.6 Hz, 2H), 8.02 (d, J=8.6 Hz,2H).

[0741] MS (ESI) mn/z 413 MH⁺

Example 723-Mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0742] Concentrated hydrochloric acid (1 mL) was added to a mixture of8-benzyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(4.7 g) which is a free compound of the compound prepared in Example 26,water-containing 5% palladium carbon (3.0 g) and ethanol (300 mL),followed by stirring at room temperature for two days in hydrogenatmosphere. After filtering through Celite, the filtrate was evaporated,which was neutralized with an aqueous solution of sodium bicarbonate.The resulting solid was filtered, and dissolved in a mixed solution ofdichloromethane, methanol and ethyl acetate. After filtering off theinsoluble matter, the mixture was purified by silica gel columncromatography (10-67% ethyl acetate/hexane), to give the title compoundas white crystals (2.6 g). 1.0 g of a raw material was recovered.

[0743]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.21 (s, 3H), 2.31 (s, 3H),2.36 (s, 3H), 3.21 (t, J=8.8 Hz, 2H), 3.94 (t, J=8.8 Hz, 2H), 5.95 (brs, 1H), 6.95 (s, 2H).

[0744] MS (ESI) m/z 307 MH⁺

Example 733-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0745] 1.0 M tert-BuOK/THF (0.29 mL, 0.29 mmol) was added to a solutionof3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(80 mg, 0.261 mmol) prepared in Example 72 in THF (4 mL), which was atroom temperature, followed by stirring at room temperature for 15 hours.Water was added, and the mixture was extracted with ethyl acetate,washed with brine, dried over MgSO₄ and the solvent was evaporated. Theresidue was subjected to silica gel column cromatography (25% ethylacetate/hexane), to give the title compound (50 mg, 63%) as whitecrystals.

[0746]¹H NMR (400 MHz, CDCl₃) δ2.05 (s, 6H), 2.32 (s, 3H), 2.34 (s, 3H),2.69 (s, 3H), 6.63 (d, J=2.9 Hz, 1H), 6.96 (d, J=3.5 Hz, 1H), 6.99 (s,2H), 11.1 (s, 1H).

[0747] MS (ESI) m/z 305 MH⁺

Example 741-(3-Mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-butanone

[0748] Triethylamine (0.091 mL, 0.652 mmol) was added to a solution of3-mesityl-2,5-dimesityl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(100 mg, 0.326 mmol) which was prepared in Example 71 in dichloromethane(4 mL), butyryl chloride (0.037 mL, 0.358 mmol) was added dropwise atroom temperature, followed by stirring for two hours. Water was added tothe reaction solution, and the mixture was extracted with ethyl acetate,washed with brine, and then dried over MgSO₄. The solvent wasevaporated, and the residue was subjected to silica gel columncromatography (7 g), to give the title compound (52 mg, 42%) as a paleyellow oil from a fraction of ethyl acetate-hexane (1:4 v/v).

[0749]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.3 Hz, 3H), 1.71-1.86 (m,2H), 2.00 (s, 6H), 2.25 (s, 3H), 2.33 (s, 3H), 2.43 (s, 3H), 2.99 (t,J=7.3 Hz, 2H), 3.06 (t, J=8.0 Hz, 2H), 4.38 (t, J=8.0 Hz, 2H), 6.97 (s,2H).

Example 758-(Butylsulfonyl)-3-mesityl2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0750] Triethylamine (0.091 mL, 0.652 mmol) was added to a solution of3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(100 mg, 0.326 mmol) prepared in Example 72 in dichloromethane (5 mL).Butanesulfonyl chloride (0.047 mL, 0.358 mmol) was added dropwise atroom temperature, followed by stirring for two hours. Water was added tothe reaction solution, extracted with ethyl acetate, washed with brine,dried over MgSO₄, and the solvent was evaporated. The residue wassubjected to silica gel column cromatography, to give the title compound(38 mg, 27%) as white crystals from a fraction of ethyl acetate-hexane(1:4 v/v).

[0751]¹H NMR (400 MHz, CDCl₃) δ1.03 (t, J=7.3 Hz, 3H), 1.54-1.65 (m,2H), 1.99 (s, 6H), 1.94-2.07 (m, 2H), 2.24 (s, 3H), 2.32 (s, 3H), 2.41(s, 3H), 3.17 (t, J=8.2 Hz, 2H), 4.34 (t, J=7.9 Hz, 2H), 4.44 (t, J=8.2Hz, 2H), 6.96 (s, 2H).

[0752] MS (ESI) m/z 427 MH⁺

Example 764-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]benzonitrile

[0753] CuCN (585 mg, 6.53 mmol) was added to a solution of3-(4-buromophenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(1.5 g, 3.63 mmol) which was prepared in Example 14 inN-methyl-2-pyrrolidinone, followed by stirring under heating underreflux for six hours. The reaction mixture was cooled to roomtemperature, water was added to the reaction solution. The resultingsolid was collected by filtration and subjected to silica gel columncromatography (100 g), to give the title compound (332 mg, 25%) as apale yellow powder from a fraction of ethyl acetate-hexane (1:2 v/v).

Example 772-Chloro-2-(2-furyl)-7,8-dihydro-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine

[0754]¹H NMR (400 MHz, DMSO-d₆) δ3.22 (t, J=6.8 Hz, 2H), 3.72 (t, J=6.8Hz, 2H), 6.71 (d, J=3.7 Hz, 1H), 7.17 (d, J=3.7 Hz, 1H), 7.93 (s, 1H),8.25 (br s, 1H).

Example 78N5-(2-Pyridylmethyl)-2-(2-furyl)-7,8-dihydro-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5-amineExample 798-(1-Ethylpropyl)-2,5-dimethyl-3-(4-methyl1,3-benzodioxol-5-yl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0755] Pale Yellow Crystals

[0756]¹H NMR (400 MHz, CDCl₃) δ0.84-1.04 (m, 6H), 1.50-1.70 (m, 4H),2.06 (s, 3H), 2.28 (s, 3H), 2.30 (s, 3H), 3.08 (t, J=9.2 Hz, 2H), 3.67(t, J=9.2 Hz, 2H), 5.58-5.72 (m, 1H), 5.97 (d, J=9.5 Hz, 2H), 6.71 (dd,J=7.9, 0.6 Hz, 1H), 6.76 (d, J=7.9 Hz, 1H).

[0757] MS (ESI) m/z 393 MH⁺

Example 808-(1Ethylpropyl)-2,5-dimethyl-3-(4-methyl-1,3-benzodioxol-5-yl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0758] Pale Yellow Amorphous

[0759]¹H NMR (400 MHz, CDCl₃) δ0.84 (t, J=7.3 Hz, 3H), 0.89 (t, J=7.3Hz, 3H), 1.76-2.05 (m, 4H), 2.09 (s, 3H), 2.37 (s, 3H), 2.66 (s, 3H),6.00 (d, J=6.0 Hz, 2H), 5.88-6.04 (m, 1H), 6.60 (d, J=3.5 Hz, 1H), 6.75(d, J=7.9 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 6.86 (d, J=3.5 Hz, 1H).

Example 812,5-Dimethyl-3-(4-methyl-1,3-benzodioxol-5-yl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0760] Pale Yellow Crystals

[0761]¹H NMR (400 MHz, CDCl₃) δ2.12 (s, 3H), 2.48 (s, 3H), 2.75 (s, 3H),6.01 (d, J=9.7 Hz, 2H), 6.64 (s, 1H), 6.77 (d, J=7.9 Hz, 1H), 6.85 (d,J=7.9 Hz, 1H), 6.98 (s, 1H), 12.90 (s, 1H).

Example 823-Mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0762] Pale Yellow Crystals

[0763]¹H NMR (400 MHz, CDCl₃) δ2.06 (s, 6H), 2.32 (d, J=1.1 Hz, 3H),2.33 (s, 3H), 2.34 (s, 3H), 2.64 (s, 3H), 6.25 (s, 1H), 6.98 (s, 2H),11.50 (s, 1H).

Example 83 3-Mesityl-2,5,8-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0764] Pale Yellow Crystals

[0765]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.26 (s, 3H), 2.33 (s, 3H),2.62 (s, 3H), 4.40 (s, 3H), 6.52 (d, J=3.6 Hz, 1H), 6.72 (d, J=3.2 Hz,1H), 6.97 (s, 2H).

[0766] MS (ESI) m/z 319 MH⁺

Example 848-Ethyl-3-mesityl-2,5,-dimetyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0767] Pale Yellow Crystals

[0768] MS (ESI) m/z 333 MH⁺

Example 853-Mesityl-2,5-dimethyl-8-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0769] Pale Yellow Crystals

[0770] MS (ESI) m/z 347 MH⁺

Example 868-Butyl-3-mesityl-2,5,-dimetyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0771] Pale Yellow Crystals

[0772] MS (ESI) m/z 361 MH⁺

Example 872-[8-(1-Ethylpropyl)-2,5,-dimetyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-5-methylphenol

[0773] White Crystals

[0774]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.2 Hz, 6H), 1.56-1.70 (m,4H), 2.33 (s, 3H), 2.34 (s, 3H), 2.56 (s, 3H), 3.10 (t, J=8.4 Hz, 2H),3.71 (t, J=8.8 Hz, 2H), 5.61-5.63 (m, 1H), 6.77 (dd, J=1.6, 7.6 Hz, 1H),6.90 (br s, 1H), 7.28 (d, J=7.6 Hz, 1H).

Example 883-Mesityl-2,5,7,8-tetramethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0775] White Crystals

[0776]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.26 (s, 3H), 2.33 (s, 3H),2.41 (s, 3H), 2.58 (s, 3H), 4.34 (s, 3H), 6.28 (s, 1H), 6.96 (s, 2H).

Example 892-(8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenylmethyl ether

[0777] Yellow Amorphous

[0778]¹H NMR (400 MHz, CDCl₃) δ0.85-0.90 (m, 6H), 1.90-2.05 (m, 4H),2.09 (s, 3H), 2.29 (s, 3H), 2.38 (s, 3H), 2.63 (s, 3H), 3.73 (s, 3H),5.88-6.03 (m, 1H), 6.57 (d, J=3.2 Hz, 1H), 6.66 (s, 1H), 6.79 (s, 1H),6.83 (d, J=3.2 Hz, 1H).

Example 903-Mesityl-2,5-dimethyl-8-pentyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinhydrochloride

[0779] White Crystals

[0780] MS (ESI) m/z 375 MH⁺

Example 918-Hexyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0781] MS (ESI) m/z 389 MH⁺

Example 928-Heptyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0782] MS (ESI) m/z 403 MH⁺

Example 933-(2-Bromo-4,6-dimethylphenyl)-8-(1-ethylpropyl)-2,5-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0783]¹H NMR (400 MHz, CDCl₃) δ0.88 (td, J=4.8 Hz, 2.8 Hz, 6H),1.82-1.93 (m, 2H), 1.95-2.02 (m, 2H), 2.09 (s, 3H), 2.30 (s, 3H), 2.34(s, 3H), 2.64 (s, 3H), 5.90-6.02 (m, 1H), 6.60 (d, J=3.6 Hz, 1H), 6.86(d, J=3.6 Hz, 1H), 7.07 (s, 1H), 7.37 (s, 1H).

[0784] MS (ESI) m/z 441 MH⁺

Example 942-Cyclobutyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0785] White Crystals

[0786]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.2 Hz, 6H), 1.60-1.70 (m,4H), 1.82-1.92 (m, 2H), 1.98 (s, 6H), 2.10-2.20 (m, 2H), 2.26 (s, 3H),2.29-2.40 (m, 2H), 2.30 (s, 3H), 3.08 (t, J=9.2 Hz, 2H), 3.29 (q, J=8.4Hz, 1H), 3.69 (t, J=9.2 Hz, 2H), 5.70-5.80 (m, 1H), 6.91 (s, 2H).

Example 953-Mesityl-2,5-dimethyl-8-phenyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0787] Yellow Crystals

[0788]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.11 (s, 3H), 2.33 (s, 3H),2.69 (s, 3H), 6.71 (d, J=3.2 Hz, 1H), 6.95 (d, J=3.2 Hz, 1H), 6.91 (s,2H), 7.49-7.56 (m, 3H), 7.60-7.66 (m, 2H).

Example 968-(2-Ethylphenyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidine

[0789] Yellow Amorphous

[0790]¹H NMR (400MHz, CDCl₃) δ1.03 (t, J=7.6 Hz, 3H), 1.98 (s, 3H), 1.99(s, 3H), 2.01 (s, 3H), 2.32 (s, 3H), 2.30-2.44 (m, 2H), 2.70 (s, 3H),6.69 (d, J=3.2 Hz, 1H), 6.80 (d, J=3.6 Hz, 1H), 6.95 (s, 2H), 7.36 (dd,J 7.6, 7.6 Hz, 1H), 7.40-7.46 (m, 2H), 7.50 (dd, J=7.2, 7.6 Hz, 1H).

Example 978-(2,6-Dimethyhlphenyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0791] Red Crystals

[0792]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.01 (s, 3H), 2.03 (s, 3H),2.32 (s, 3H), 2.70 (s, 3H), 6.70 (d, J=3.2 Hz, 1H), 6.73 (d, J=3.6 Hz,1H), 6.95 (s, 2H), 7.21 (d, J=7.6 Hz, 2H), 7.34 (dd, J=7.6, 7.6 Hz, 1H).

Example 983-Mesityl-2,5-dimethyl-8-(1-propylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0793] Brown Oil

[0794]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.2 Hz, 6H), 1.05-1.20 (m,4H), 1.80-1.94 (m, 4H), 2.03 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H), 2.62(s, 3H), 6.12-6.20 (m, 1H), 6.58 (d, J=3.6 Hz, 1H), 6.86 (d, J=3.6 Hz,1H), 6.97 (s, 2H).

Example 992-Cyclopropyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0795] Brown Oil

[0796]¹H NMR (400 MHz, CDCl₃) δ0.84-0.92 (m, 8H), 1.01-1.03 (m, 2H),1.65-1.75 (m, 1H), 1.90-2.00 (m, 4H), 2.11 (s, 6H), 2.34 (s, 3H), 2.61(s, 3H), 5.75-5.90 (m, 1H), 6.57 (d, J=3.6 Hz, 1H), 6.83 (d, J=3.6 Hz,1H), 6.98 (s, 2H).

Example 1008-(1-Ethylpropyl)-3-mesityl-5-methyl-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0797] Brown Oil

[0798]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.2 Hz, 6H), 1.80-2.10 (m,4H), 2.14 (s, 6H), 2.33 (s, 3H), 2.67 (s, 3H), 5.88-6.00 (m, 1H), 6.64(d, J=3.2 Hz, 1H), 6.92 (d, J=3.6 Hz, 1H), 6.98 (s, 2H), 7.87 (s, 1H).

Example 1012-Ethyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidine

[0799] Brown Oil

[0800]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.2 Hz, 6H), 1.19 (t, J=7.6Hz, 3H), 1.80-2.01 (m, 4H), 2.03 (s, 6H), 2.33 (s, 3H), 2.59 (q, J=7.6Hz, 2H), 2.62 (s, 3H), 5.90-6.10 (m, 1H), 6.59 (d, J=3.6 Hz, 1H), 6.85(d, J=3.2 Hz, 1H), 6.97 (s, 2H).

Example 1028-(2,3-Dihydro-1H-2-indenyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0801] White Crystals

[0802]¹H NMR (400 MHz, CDCl₃) δ2.04 (s, 6H), 2.26 (s, 3H), 2.34 (s, 3H),2.61 (s, 3H), 3.33 (dd, J=4.8, 16.4 Hz, 2H), 3.72 (dd, J=8.0, 16.4 Hz,2H), 6.47 (d, J=3.2 Hz, 1H), 6.69 (d, J=3.6 Hz, 1H), 6.96-7.00 (m, 3H),7.25-7.33 (m, 4H).

Example 103N-5-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-4-methyl-2-pyridyl-N,N-dimethylamine

[0803] White Crystals

[0804]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.6 Hz, 6H), 1.80-2.02 (m,4H), 2.19 (s, 3H), 2.38 (s, 3H), 2.65 (s, 3H), 3.12 (s, 6H), 5.90-6.02(m, 1H), 6.51 (s, 1H), 6.60 (d, J=3.6 Hz, 1H), 6.85 (d, J=3.2 Hz, 1H),8.07 (s, 1H).

Example 1043-(4-Bromo-2,6-dimethylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0805] White Crystals

[0806]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.4 Hz, 6H), 1.53-1.74 (m,4H), 2.03 (s, 6H), 2.13 (s, 3H), 2.27 (s, 3H), 3.09 (t, J=9.2 Hz, 2H),3.68 (t, J=9.2 Hz, 2H), 5.56-5.70 (m, 1H), 7.25 (s, 2H).

Example 1053-(4-Bromo-2,6-dimethylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0807] White Crystals

[0808]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.3 Hz, 6H), 1.70-2.10 (m,4H), 2.05 (s, 6H), 2.22 (s, 3H), 2.64 (s, 3H), 5.82-6.04 (m, 1H), 6.61(d, J=3.2 Hz, 1H), 6.87 (d, J=3.5 Hz, 1H), 7.95 (s, 2H).

Example 1064-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylbenzaldehyde

[0809] Yellow Amorphous

[0810]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.3 Hz, 6H), 1.52-1.74 (m,4H), 2.15 (s, 3H), 2.16 (s, 6H), 2.28 (s, 3H), 3.10 (t, J=9.2 Hz, 2H),3.70 (t, J=9.1 Hz, 2H), 5.56-5.71 (m, 1H), 7.62 (s, 2H), 9.98 (s, 1H).

Example 1071-4-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylphenyl-1-ethanone

[0811] Pale Yellow Crystals

[0812]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.4 Hz, 6H), 1.50-1.74 (m,4H), 2.13 (s, 6H), 2.14 (s, 3H), 2.27 (s, 3H), 2.60 (s, 3H), 3.09 (t,J=9.2 Hz, 2H), 3.69 (t, J=9.2 Hz, 2H), 5.55-5.72 (m, 1H), 7.71 (s, 2H).

Example 1081-4-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylphenyl-1-ethanone

[0813] White Crystals

[0814]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.3 Hz, 6H), 1.80-2.08 (m,4H), 2.14 (s, 6H), 2.23 (s, 3H), 2.62 (s, 3H), 2.64 (s, 3H), 5.88-6.02(m, 1H), 6.61 (d, J=3.5 Hz, 1H), 6.88 (d, J=3.5 Hz, 1H), 7.74 (s, 2H).

Example 1098-(1-Ethylpropyl)-3-(4-isopropenyl-2,5-dimethylphenyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrmidine

[0815] White Crystals

[0816]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.4 Hz, 6H), 1.80-2.09 (m,4H), 2.10 (s, 6H), 2.19 (s, 3H), 2.26 (s, 3H), 2.64 (s, 3H), 5.07 (s,1H), 5.41 (s, 1H), 5.86-6.06 (m, 1H), 6.61 (d, J=3.5 Hz, 1H), 6.87 (d,J=3.5 Hz, 1H), 7.27 (s, 2H).

Example 1102-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine-3-yl]-3,5-dimethylphenol

[0817] Yellowish White Amorphous

[0818]¹H NMR (400 MHz, CDCl₃) δ0.85-0.90 (m, 6H), 1.80-1.92 (m, 2H),1.92-2.05 (m, 2H), 2.12 (s, 3H), 2.33 (s, 3H), 2.34 (s, 3H), 2.67 (s,3H), 5.93 (br s, 1H), 6.63 (d, J=3.6 Hz, 1H), 6.75 (s, 2H), 6.89 (d,J=3.2 Hz, 1H).

Example 1112-(3-Mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylmethyl ether

[0819] Yellowish Brown Crystals

[0820]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 3H), 2.22 (s, 3H), 2.30 (s, 3H),2.46 (s, 3H), 2.61 (s, 3H), 3.36 (s, 3H), 3.89 (t, J=5.6 Hz, 2H), 4.87(t, J=5.6 Hz, 2H), 6.27 (s, 1H), 6.92 (s, 2H).

Example 1122-(8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenylmethanesulfonate

[0821] Yellow Oil

[0822]¹H NMR (400 MHz, CDCl₃) δ0.81-0.91 (m, 6H), 1.80-1.94 (m, 2H),1.94-2.04 (m, 2H), 2.16 (s, 3H), 2.32 (s, 3H), 2.39 (s, 3H), 2.40 (s,3H), 2.64 (s, 3H), 5.95 (br s, 1H), 6.61 (d, J=3.6 Hz, 1H), 6.89 (d,J=3.6 Hz, 1H), 7.12 (d, J=4.0 Hz, 1H), 7.19 (d, J=4.0 Hz, 1H).

Example 1138-Benzyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0823] Grayish White Crystals

[0824] MS (ESI) m/z 395 MH⁺

Example 1143-(2-Bromo-4,6-dimethylphenyl)-8-(2-methoxyethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0825] White Crystals

[0826] MS (ESI) m/z 427, 429 MH⁺

Example 1153-Mesityl-2,5-dimethyl-8-(2-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0827] Brown Crystals

[0828]¹H NMR (400 MHz, CDCl₃) δ1.92 (s, 6H), 2.11 (s, 3H), 2.30 (s, 3H),2.66 (s, 3H), 6.23 (s, 2H), 6.89 (d, J=3.6 Hz, 1H), 6.98 (s, 2H), 7.32(d, J=3.6 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.45 (dd, J=7.2 Hz, 4.8 Hz,1H), 7.94 (dd, J=7.2 Hz, 7.2 Hz, 1H), 8.59 (d, J=4.8 Hz, 1H).

[0829] MS (ESI) m/z 396 MH⁺

Example 1163-Mesityl-2,5-dimethyl-8-(3-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0830] Pale Yellow Crystals

[0831] MS (ESI) m/z 396 MH⁺

Example 1173-Mesityl-2,5-dimethyl-8-(4-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0832] Pale Yellow Crystals

[0833] MS (ESI) m/z 396 MH⁺

Example 118 Ethyl2-(2-(8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenoxy)acetate

[0834] Yellowish White Crystals

[0835]¹H NMR (400 MHz, CDCl₃) δ0.85-0.91 (m, 6H), 1.21 (t, J=7.2 Hz,3H), 1.79-1.93 (m, 2H), 1.93-2.03 (m, 2H), 2.11 (s, 3H), 2.35 (s, 3H),2.36 (s, 3H), 2.63 (s, 3H), 4.16 (q, J=7.2 Hz, 2H), 4.45 (d, J=16.4 Hz,1H), 4.51 (d, J=16.0 Hz, 1H), 5.98 (br s, 1H), 6.55 (s, 1H), 6.58 (d,J=3.2 Hz, 1H), 6.82-6.86 (m, 1H), 6.84 (s, 1H).

Example 1191-(2-(8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenoxy)-2-methyl-2-propanol

[0836] Yellow Amorphous

[0837]¹H NMR (400 MHz, CDCl₃) δ0.78 (t, J=7.2 Hz, 3H), 0.84 (s, 3H),0.91 (t, J=7.6 Hz, 3H), 1.02 (s, 3H), 1.70-1.85 (m, 2H), 1.85-2.03 (m,2H), 2.12 (s, 3H), 2.29 (s, 3H), 2.36 (s, 3H), 2.64 (s, 3H), 3.68 (d,J=8.8 Hz, 1H), 3.80 (d, J=9.2 Hz, 1H), 5.98 (br s, 1H), 6.60 (d, J=3.6Hz, 1H), 6.63 (s, 1H), 6.79 (s, 1H), 6.85 (d, J=3.6 Hz, 1H).

Example 120(2-(8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenoxy)methylcyanide

[0838] Pale Orange Crystals

[0839]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.2 Hz, 6H), 1.79-1.92 (m,2H), 1.92-2.03 (m, 2H), 2.11 (s, 3H), 2.29 (s, 3H), 2.39 (s, 3H), 2.64(s, 3H), 4.57 (s, 2H), 5.94 (br s, 1H), 6.60 (d, J=3.6 Hz, 1H), 6.79 (s,1H), 6.60 (d, J=3.6 Hz, 1H), 6.94 (s, 1H).

Example 1212-(2-(8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidin-3-yl)-3,5-dimethylphenoxy)acetamide

[0840] Yellow Amorphous

[0841]¹H NMR (400 MHz, CDCl₃) δ0.876 (t, J=7.2 Hz, 3H), 0.880 (t, J=7.2Hz, 3H), 1.80-1.92 (m, 2H), 1.92-2.06 (m, 2H), 2.13 (s, 3H), 2.33 (s,3H), 2.37 (s, 3H), 2.57 (s, 3H), 4.39 (d, J=16.0 Hz, 1H), 4.56 (d,J=16.4 Hz, 1H), 5.46 (br s, 1H), 5.96 (br s, 1H), 6.61 (d, J=3.6 Hz,1H), 6.63 (s, 1H), 6.84 (s, 1H), 6.88 (d, J=3.2 Hz, 1H), 8.32 (br s,1H).

Example 1223-(2,4-Dimethoxy-6-methylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0842] Pale Yellow Crystals

[0843]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.2 Hz, 3H), 0.88 (t, J=7.2Hz, 3H), 1.80-2.02 (m, 4H), 2.11 (s, 3H), 2.27 (s, 3H), 2.63 (s, 3H),3.72 (s, 3H), 3.85 (s, 3H), 5.90-6.02 (m, 1H), 6.43 (d, J=2.8 Hz, 1H),6.51 (d, J=2.4 Hz, 1H), 6.57 (d, J=3.6 Hz, 1H), 6.83 (d, J=3.6 Hz, 1H).

Example 1233-(2-Bromo-4,6-dimethylphenyl)-8-[1-(methoxymethylpropyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0844] MS (ESI) m/z 455, 457 MH⁺

Example 1243-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-8-(1-propylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0845] MS (ESI) m/z 469 MH⁺

Example 1253-Mesityl-2,5-dimethyl-8-neopentyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0846] Brown Oil

[0847]¹H NMR (400 MHz, CDCl₃) δ1.04 (s, 9H), 2.02 (s, 6H), 2.25 (s, 3H),2.33 (s, 3H), 2.63 (s, 3H), 4.72 (s, 2H), 6.53 (d, J=3.6 Hz, 1H), 6.76(d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1268-(1-Ethylbutyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0848] Brown Oil

[0849]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.6 Hz, 3H), 0.91 (t, J=7.2Hz, 3H), 1.13-1.40 (m, 2H), 1.80-2.00 (m, 4H), 2.03 (s, 6H), 2.24 (s,3H), 2.33 (s, 3H), 2.62 (s, 3H), 6.00-6.13 (m, 1H), 6.59 (d, J=3.6 Hz,1H), 6.85 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1278-(1,3-Dimethylbutyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0850] Brown Oil

[0851]¹H NMR (400 MHz, CDCl₃) δ0.95 (d, J=6.8 Hz, 3H), 0.96 (d, J=6.4Hz, 3H), 1.44-1.52 (m, 1H), 1.56 (d, J=6.8 Hz, 3H), 1.60-1.68 (m, 2H),1.85-1.93 (m, 1H), 2.03 (s, 3H), 2.03 (s, 3H), 6.20-6.30 (m, 1H), 6.57(d, J=3.6 Hz, 1H), 6.90 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1283-Mesityl-2,5-dimethyl-8-(1-methylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0852] Brown Oil

[0853]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 3H), 1.20-1.43 (m,2H), 1.58 (d, J=7.2 Hz, 3H), 1.80-1.97 (m, 2H), 2.04 (s, 3H), 2.04 (s,3H), 2.25 (s, 3H), 2.33 (s, 3H), 2.61 (s, 3H), 6.12-6.20 (m, 1H), 6.57(d, J=3.6 Hz, 1H), 6.90 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1293-Mesityl-2,5-dimethyl-8-(2-methylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0854] Brown Oil

[0855]¹H NMR (400 MHz, CDCl₃) δ0.95 (d, J=6.8 Hz, 3H), 1.00 (t, J=7.2Hz, 3H), 1.25-1.37 (m, 1H), 1.43-1.58 (m, 1H), 2.03 (s, 3H), 2.03 (s,3H), 2.05-2.20 (m, 1H), 2.24 (s, 3H), 2.33 (s, 3H), 2.62 (s, 3H), 4.48(dd, J=8.0, 13.6 Hz, 1H), 4.74 (dd, J=6.8, 13.6 Hz, 1H), 6.52 (d, J=3.2Hz, 1H), 6.74 (d, J=3.2 Hz, 1H), 6.97 (s, 2H).

Example 1302-(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl-)ethylmethyl ether

[0856] Yellowish Brown Oil

[0857]¹H NMR (400 MHz, CDCl₃) δ1.09 (t, J=7.2 Hz, 3H), 1.75-1.82 (m,2H), 2.03 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.77 (t,J=7.2 Hz, 2H), 3.36 (s, 3H), 3.88 (t, J=5.6 Hz, 2H), 4.89 (t, J=5.6 Hz,2H), 6.26 (s,1H), 6.97 (s, 2H).

Example 1318-(1-Ethylpropyl)-3-(2-isopropenyl-4,6-dimethylphenyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0858]¹H NMR (400 MHz, CDCl₃) δ0.86 (t, J=7.3 Hz, 3H), 0.88 (t, J=7.3Hz, 3H), 1.62 (s, 3H), 1.80-2.03 (m, 4H), 2.05 (s, 3H), 2.21 (s, 3H),2.36 (s, 3H), 2.62 (s, 3H), 4.79 (s, 1H), 4.80 (s, 1H), 5.86-6.04 (m,1H), 6.59 (d, J=3.5 Hz, 1H), 6.85 (d, J=3.5 Hz, 1H), 6.98 (s, 1H), 7.05(s, 1H).

Example 1323-Mesityl-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0859] White Crystals

[0860] MS (ESI) m/z 391 MH⁺

Example 1338-Isopentyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0861] Brown Oil

[0862]¹H NMR (400 MHz, CDCl₃) δ1.04 (d, J=6.8 Hz, 6H), 1.65-1.80 (m,1H), 1.84-1.90 (m, 2H), 2.03 (s, 6H), 2.25 (s, 3H), 2.34 (s, 3H), 2.62(s, 3H), 4.79-4.83 (m, 2H), 6.53 (d, J=3.2 Hz, 1H), 6.78 (d, J=3.2 Hz,1H), 6.98 (s, 2H).

Example 1343-(2,6-Dimethoxy-4-methylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0863] Pale Brown Crystals

[0864]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.2 Hz, 6H), 1.80-2.00 (m,4H), 2.32 (s, 3H), 2.42 (s, 3H), 2.62 (s, 3H), 3.75 (s, 6H), 6.52 (s,2H), 6.55 (d, J=3.2 Hz, 1H), 6.81 (d, J=3.2 Hz, 1H).

Example 1352-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether

[0865] White Crystals

[0866]¹H NMR (400 MHz, CDCl₃) δ1.63 (d, J=7.2 Hz, 3H), 2.02 (s, 6H),2.24 (s, 3H), 2.33 (s, 3H), 2.62 (s, 3H), 3.39 (s, 3H), 3.70-3.82 (m,2H), 6.30-6.40 (m, 1H), 6.56 (d, J=3.6 Hz, 1H), 6.97 (s, 2H), 7.01 (d,J=3.6 Hz, 1H).

Example 1363-(2-Bromo-4,6-dimethylphenyl)-8-(1-ethylbutyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0867] Brown Oil

[0868]¹H NMR (400MHz, CDCl₃) δ0.83-0.93 (m, 6H), 1.10-1.40 (m, 2H),1.80-2.00 (m, 4H), 2.09 (s, 3H), 2.29 (s, 3H), 2.34 (s, 3H), 2.64 (s,3H), 6.00-6.10 (m, 1H), 6.59 (d, J=3.2 Hz, 1H), 6.86 (d, J=3.6 Hz, 1H),7.07 (br s, 1H), 7.37 (br s, 1H).

Example 1378-(1,2-Dimethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0869] White Crystals

[0870]¹H NMR (400 MHz, CDCl₃) δ0.85 (d, J=6.8 Hz, 3H), 1.06 (d, J=6.8Hz, 3H), 1.58 (d, J=6.8 Hz, 3H), 2.02 (s, 3H), 2.04 (s, 3H), 2.05-2.20(m, 1H), 2.25 (s, 3H), 2.33 (s, 3H), 2.62 (s, 3H), 5.85-5.96 (m, 1H),6.57 (d, J=3.2 Hz, 1H), 6.89 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1382-(7-Ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethyl methyl ether

[0871] Reddish White Crystals

[0872]¹H NMR (400 MHz, CDCl₃) δ1.38 (t, J=7.6 Hz, 3H), 2.03 (s, 6H),2.24 (s,3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.82 (q, J=7.6 Hz, 2H), 3.36(s, 3H), 3.88 (t, J=6.0 Hz, 2H), 4.88 (t, J=5.6 Hz, 2H), 6.27 (s, 1H),6.97 (s, 2H).

Example 1398-Butyl-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0873] Yellow Oil

[0874]¹H NMR (400 MHz, CDCl₃) δ1.02 (t, J=7.2 Hz, 3H), 1.09 (t, J=7.6Hz, 3H), 1.43-1.53 (m, 2H), 1.75-1.83 (m, 2H), 1.83-1.92 (m, 2H), 2.03(s, 3H), 2.25 (s, 3H), 2.33 (s, 3H), 2.59 (s, 3H), 2.70 (t, J=7.6 Hz,2H), 4.72 (t, J=7.6 Hz, 2H), 6.26 (s, 1H), 6.97 (s, 2H).

Example 1403-Mesityl-2,5,8-trimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0875] White Amorphous

[0876]¹H NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.74-1.80 (m,2H), 2.02 (s, 6H), 2.27 (s, 3H), 2.33 (s, 3H), 2.59 (s, 3H), 2.68 (t,J=7.6 Hz, 2H), 4.35 (s, 3H), 6.27 (s, 1H), 6.97 (s, 2H).

Example 1418-(1-Ethylpropyl)-3-(2-isopropenyl-4,6-dimethylphenyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0877]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.4 Hz, 3H), 0.93 (t, J=7.4Hz, 3H), 1.07 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.9 Hz, 3H), 1.80-2.08 (m,4H), 1.99 (s, 3H), 2.24 (s, 3H), 2.38 (s, 3H), 2.61 (s, 3H), 2.65-2.80(m, 1H), 5.84-6.07 (m, 1H), 6.59 (dd, J=3.3, 1.0 Hz, 1H), 6.86 (dd,J=3.3, 1.0 Hz, 1H), 6.98 (s, 1H), 7.06 (s, 1H).

Example 1422-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-butanol

[0878] Brown Amorphous

[0879]¹H NMR (400 MHz, CDCl₃) δ1.03 (t, J=7.2 Hz, 3H), 1.90-2.10 (m,2H), 2.04 (s, 6H), 2.24 (s, 3 H), 2.33 (s, 3H), 2.63 (s, 3H), 3.60 (br s1H), 3.80-3.85 (m, 1H), 4.10-4.17 (m, 1H), 5.80-5.90 (m, 1H), 6.63 (d,J=3.6 Hz, 1H), 6.95 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1432-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-pentanol

[0880] Brown Amorphous

[0881]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=7.2 Hz, 3H), 1.33-1.45 (m,2H), 1.90-2.10 (m, 2H), 1.99 (s, 3H), 2.05 (s, 3H), 2.24 (s, 3H), 2.33(s, 3H), 2.63 (s, 3H), 3.82 (dd, J=8.8, 11.2 Hz, 1H), 4.04-4.14 (m, 1H),5.95-6.05 (m, 1H), 6.63 (d, J=3.6 Hz, 1H), 6.95 (d, J=3.6 Hz, 1H), 6.97(s, 2H).

Example 1448-(1-Ethylpropyl)-3-(2-isopropyl-4,6-dimethylphenyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0882] White Crystals

[0883]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.4 Hz, 6H), 1.27 (d, J=7.0Hz, 6H), 1.80-2.04 (m,4H), 2.05 (s, 6H), 2.24 (s, 3H), 2.63 (s, 3H),2.81-2.93 (m, 1H), 5.88-6.04 (m, 1H), 6.59 (d, J=3.5 Hz, 1H), 6.85 (d,J=3.5 Hz, 1H), 6.98 (s, 2H).

Example 1451-2-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylphenylethylmethyl ether

[0884] Yellow Crystals

[0885]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.3 Hz, 3H), 0.92 (t, J=7.3Hz, 3H), 1.14 (d, J=6.4 Hz, 2H), 1.30 (d, J=6.4 Hz, 1H), 1.80-2.04 (m,4H), 2.02 (s, 2H), 2.05 (s, 1H), 2.22 (s, 2H), 2.24 (s, 1H), 2.40 (s,3H), 2.59 (s, 3H), 3.11 (s, 1H), 3.22 (s, 2H), 4.10-4.18 (m, 1H),5.87-6.02 (m, 1H), 6.60 (d, J=3.3 Hz, 1H), 6.88 (d, J=3.3 Hz, 1H), 7.06(s, 1H), 7.25 (s, 1H).

Example 1461-2-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylphenylethylmethyl ether

[0886] Yellow Oil

[0887]¹H NMR (400 MHz, CDCl₃) δ0.90-1.02 (m, 6H), 1.13 (d, J=6.4 Hz,2H), 1.30 (d, J=6.4 Hz, 1H), 1.52-1.78 (m, 4H), 2.00 (s, 2H), 2.05 (s,1H), 2.14 (s, 2H), 2.16 (s, 1H), 2.23 (s, 3H), 2.37 (s, 3H), 3.10 (s,1H), 3.21 (s, 2H), 3.09 (t, J=8.8 Hz, 2H), 3.69 (t, J=8.8 Hz, 2H),4.08-4.18 (m, 1H), 5.57-5.69 (m, 1H), 7.02 (s, 1H), 7.18 (s, 0.34H),7.20 (s, 0.66H).

Example 1478-(sec-Butyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0888] Pale Yellow Crystals

[0889]¹H NMR (400 MHz, CDCl₃) δ0.92 (t, J=7.6 Hz, 3H), 1.59 (d, J=6.4Hz, 3H), 1.90-2.00 (m, H), 2.02 (s, 3H), 2.04 (s, 3H), 2.25 (s, 3H),2.33 (s, 3H), 2.62 (s, 3H), 6.02-6.08 (m, 1H), 6.58 (d, J=3.6 Hz, 1H),6.90 (d, J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1482-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-hexanol

[0890] Pale Brown Crystals

[0891]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.2 Hz, 3H), 1.25-1.42 (m,4H), 1.90-2.00 (m, 2H), 1.99 (s, 3H), 2.04 (s, 3H), 2.24 (s, 3H), 2.33(s, 3H), 2.63 (s, 3H), 3.60 (br s, 1H), 3.74-3.84 (m, 1H), 4.12 (dd,J=3.2, 11.2 Hz, 1H), 5.90-6.00 (m, 1H), 6.62 (d, J=3.2 Hz, 1H), 6.95 (d,J=3.6 Hz, 1H), 6.97 (s, 2H).

Example 1493-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-8-(1-methylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0892] White Amorphous

[0893]¹H NMR (400 MHz, CDCl₃) δ0.95 (dt, J=7.4, 4.4 Hz, 3H), 1.27 (dd,J=4.4, 2.2 Hz, 3H), 1.30-1.59 (m, 4H), 2.08 (s, 3H), 2.21 (s, 3H), 2.27(s, 3H), 2.31 (s, 3H), 3.05 (t, J=9.2 Hz, 2H), 3.74 (t, J=9.2 Hz, 2H),5.80-5.93 (m, 1H), 7.03 (s, 1H), 7.33 (s, 1H).

Example 1503-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-8-(1-methylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0894] White Amorphous

[0895]¹H NMR (400 MHz, CDCl₃) δ0.93 (dt, J=7.3, 2.0 Hz, 3H), 1.18-1.48(m, 2H), 1.57 (dd, J=6.8, 2.4 Hz, 3H), 1.77-1.98 (m, 2H), 2.08 (d, J=8.4Hz, 3H), 2.30 (s, 3H), 2.34 (s, 3H), 2.63 (s, 3H), 6.10-6.22 (m, 1H),6.58 (d, J=3.5 Hz, 1H), 6.91 (d, J=3.5 Hz, 1H), 7.07 (s, 1H), 7.37 (s,1H).

Example 1513-(2-Bromo-4,6-dimethylphenyl-4,6-dimethybutyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0896] Pale Yellow Amorphous

[0897]¹H NMR (400 MHz, CDCl₃) δ0.96 (d, J=2.2 Hz, 3H), 0.98 (d, J=6.0Hz, 3H), 1.26 (dd, J=5.3, 1.3 Hz, 3H), 1.31-1.42 (m, 1H), 1.53-1.70 (m,2H), 2.08 (s, 3H), 2.20 (s, 3H), 2.27 (s, 3H), 2.31 (s, 3H), 3.05 (t,J=9.5 Hz, 2H), 3.62-3.80 (m, 2H), 5.93-6.05 (m, 1H), 7.03 (s, 1H), 7.33(s, 1H).

Example 1523-(2-Bromo-4,6-dimethylphenyl)-8-(1,3-dimethylbutyl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0898] Pale Brown Amorphous

[0899]¹H NMR (400 MHz, CDCl₃) δ0.91-1.00 (m, 6H), 1.40-1.70 (m, 2H), 1,55 (dd, J=6.6, 2.9 Hz, 3H), 1.83-1.94 (m, 1H), 2.08 (s, 3H), 2.29 (s,3H), 2.34 (s, 3H), 2.63 (s, 3H), 6.20-6.32 (m, 1H), 6.58 (d, J=3.5 Hz,1H), 6.91 (d, J=3.5 Hz, 1H), 7.07 (s, 1H), 7.37 (s, 1H).

Example 1533-(2-Bromo-4,6-dimethylphenyl)-8-(1,2-dimethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0900] Pale Yellow Amorphous

[0901]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=6.1 Hz, 3H), 1.04 (d, J=6.8Hz, 3H), 1.30 (dd, J=5.0, 1.7 Hz, 3H), 1.79-1.92 (m, 1H), 2.08 (s, 3H),2.21 (s, 3H), 2.72 (s, 3H), 2.31 (s, 3H), 3.06 (t, J=9.2 Hz, 2H),3.64-3.84 (m, 2H), 5.48-5.62 (m, 1H), 7.03 (s, 1H), 7.33 (s, 1H).

Example 1543-(2-Bromo-4,6-dimethylphenyl)-8-(1,2-dimethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0902] Pale Yellow Amorphous

[0903]¹H NMR (400 MHz, CDCl₃) δ0.86 (t, J=6.5 Hz, 3H), 1.05 (d, J=6.8Hz, 3H), 1, 57 (dd, J=4.2, 2.7 Hz, 3H), 2.07 (s, 3H), 2.00-2.20 (m, 1H),2.30 (s, 3H), 2.34 (s, 3H), 2.64 (s, 3H), 5.84-5.98 (m, 1H), 6.57 (dd,J=3.5, 1.1 Hz, 1H), 6.89 (d, J=3.3 Hz, 1H), 7.07 (s, 1H), 7.37 (s, 1H).

Example 1552-[3-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]propylmethyl ether

[0904] Yellow Amorphous

[0905]¹H NMR (400 MHz, CDCl₃) δ1.30 (t, J=6.9 Hz, 3H), 2.06 (d, J=6.0Hz, 3H), 2.21 (s, 3 H), 2.28 (s, 3H), 2.31 (s, 3H), 3.00-3.12 (m, 2H),3.37 (d, J=7.3 Hz, 3H), 3.47-3.55 (m, 1H), 3.58-3.67 (m, 1H), 3.76-3.86(m, 2H), 6.05-6.18 (m, 1H), 7.03 (s, 1H), 7.33 (s, 1H).

Example 1562-[3-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]propylmethyl ether

[0906] Pale Yellow Amorphous

[0907]¹H NMR (400 MHz, CDCl₃) δ1.63 (dd, J=7.1, 4.1 Hz, 3H), 2.08 (s,3H), 2.30 (s, 3H), 2.34 (s, 3H), 2.64 (s, 3H), 3.70-3.84 (m, 2H),6.29-6.42 (m, 1H), 6.57 (d, J=3.5 Hz, 1H), 7.02 (dd, J=4.8, 3.5 Hz, 1H),7.07 (s, 1H), 7.37 (s, 1H).

Example 1573-(2-Bromo-4,6-dimethylphenyl)-8-isopentyl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0908] Pale Yellow Amorphous

[0909]¹H NMR (400 MHz, CDCl₃) δ1.01 (d, J=6.6 Hz, 6H), 1.58-1.67 (m,2H), 1.67-1.79 (m, 1H), 2.08 (s, 3H), 2.22 (s, 3H), 2.28 (s, 3H), 2.31(s, 3H), 3.07 (dd, J=10.0, 8.2 Hz, 2H), 3.68-3.84 (m, 2H), 4.10-4.23 (m,1H), 4.24-4.38 (m, 1H), 7.03 (s, 1H), 7.33 (s, 1H).

Example 1583-(2-Bromo-4,6-dimethylphenyl)-8-isopentyl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0910] White Amorphous

[0911]¹H NMR (400 MHz, CDCl₃) δ1.03 (d, J=5.5 Hz, 6 H), 1.67-1.79 (m,1H), 1.82-1.91 (m, 2H), 2.09 (s, 3H), 2.31 (s, 3H), 2.34 (s, 3H), 2.63(s, 3H), 4.71-4.90 (m, 2H), 6.53 (d, J=3.3 Hz, 1H), 6.78 (d, J=3.5 Hz,1H), 7.07 (s, 1H), 7.37 (s, 1H).

Example 1593-(2-Bromo-4,6-dimethylphenyl)-8-(sec-butyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0912] Yellow Crystals

[0913]¹H NMR (400 MHz, CDCl₃) δ0.98 (td, J=7.3, 5.3 Hz, 3H), 1.28 (dd,J=6.6, 4.0 Hz, 3H), 1.54-1.74 (m, 2H), 2.08 (s, 3H), 2.22 (s, 3H), 2.28(s, 3H), 2.31 (s, 3H), 3.06 (t, J=9.2 Hz, 2H), 3.63-3.80 (m, 2H),5.68-5.82 (m, 1H), 7.03 (s, 1H), 7.33 (s, 1H).

Example 1603-(2-Bromo-4,6-dimethylphenyl)-8-(sec-butyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0914] Yellow Crystals

[0915]¹H NMR (400 MHz, CDCl₃) δ0.92 (t d, J=7.3, 3.1 Hz, 3H), 1.58 (dd,J=6.8, 1.7 Hz, 3H), 1.87-2.00 (m, 2H), 2.08 (d, J=7.5 Hz, 3H), 2.31 (s,3H), 2.34 (s, 3H), 2.64 (s, 3H), 5.95-6.12 (m, 1H), 6.58 (d, J=3.5 Hz,1H), 6.91 (d, J=3.5 Hz, 1H), 7.07 (s, 1H), 7.37 (s, 1H).

Example 1613-Mesityl-2,5-dimethyl-8-(1-phenylethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0916] Brown Amorphous

[0917] MS (ESI) m/z 409 MH⁺

Example 1622-(7-Isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylmethyl ether

[0918] White Crystals

[0919]¹H NMR (400 MHz, CDCl₃) δ1.35 (d, J=6.8 Hz, 6H), 2.02 (s, 6H),2.24 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 3.15-3.27 (m, 1H), 3.35 (s,3H), 3.86 (t, J=5.6 Hz, 2H), 4.94 (t, J=5.6 Hz, 2H), 6.29 (s, 1H), 6.97(s, 2H).

Example 1638-Isopentyl-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0920] Yellow Crystals

[0921]¹H NMR (400 MHz, CDCl₃) δ1.07 (d, J=6.4 Hz, 6H), 1.09 (t, J=7.2Hz, 3H), 1.72-1.86 (m, 5H), 2.03 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H),2.59 (s, 3H), 2.70 (t, J=8.0 Hz, 2H), 4.73 (t, J=6.4 Hz, 2H), 6.26 (s,1H), 6.96 (s, 2H).

Example 1648-(1-Benzylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0922] White Crystals

[0923]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.2 Hz, 3H), 1.90-2.07 (m,2H), 2.00 (s, 3H), 2.03 (s, 3H), 2.24 (s, 3H), 2.33 (s, 3H), 2.60 (s,3H), 3.08-3.23 (m, 2H), 6.20-6.38 (m, 1H), 6.57 (d, J=3.6 Hz, 1H), 6.86(br s, 1H), 6.96 (s, 2H), 7.01-7.15 (m, 5H).

Example 165N-5-[2,5-Dimethyl-8-(1-propylbutyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-4-methyl-2-pyridyl-N,N-dimethylamine

[0924] Brown Oil

[0925]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.2 Hz, 6H), 1.05-1.40 (m,4H), 1.78-1.86 (m, 4H), 2.19 (s, 3H), 2.38 (s, 3H), 2.64 (s, 3H), 3.12(s, 6H), 6.13-6.20 (m, 1H), 6.51 (s, 1H), 6.59 (d, J=3.6 Hz, 1H), 6.86(d, J=3.6 Hz, 1H), 8.08 (s, 1H).

Example 1662-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)hexyl methyl ether

[0926] Yellow Oil

[0927]¹H NMR (400 MHz, CDCl₃) δ0.85 (t, J=7.2 Hz, 3H), 1.15-1.42 (m,4H), 1.90-2.02 (m, 2H), 2.02 (s, 3H), 2.03 (s, 3H), 2.23 (s, 3H), 2.33(s, 3H), 2.61 (s, 3H), 3.37 (s, 3H), 3.73-3.83 (m, 2H), 6.20-6.36 (m,1H), 6.57 (d, J=3.6 Hz, 1H), 6.97 (s, 2H), 7.00 (d, J=3.6 Hz, 1H).

Example 1678-(Cyclopropylmethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0928] Yellow Oil

[0929]¹H NMR (400 MHz, CDCl₃) δ0.49-0.54 (m, 2H), 0.60-0.64 (m, 2H),1.10 (t, J=7.2 Hz, 3H), 1.29-1.40 (m, 1H), 1.77-1.87 (m, 2H), 2.02 (s,6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.61 (s, 3H), 2.75 (t, J=7.6 Hz, 2H),4.73 (d, J=6.8 Hz, 2H), 6.31 (s, 1H), 6.97 (s, 2H).

Example 1683-(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether

[0930] Yellow Oil

[0931]¹H NMR (400 MHz, CDCl₃) δ1.09 (t, J=7.2 Hz, 3H), 1.74-1.84 (m,2H), 2.02 (s, 3H), 2.16-2.24 (m, 2H), 2.33 (s, 3H), 2.60 (s, 3H), 2.73(t, J=7.2 Hz, 2H), 3.35 (s, 3H), 3.47 (t, J=6.0 Hz, 2H), 4.80 (t, J=6.8Hz, 2H), 6.27 (s, 1H), 6.97 (s, 2H).

Example 1692-(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylcyanide

[0932] Yellow Oil

[0933]¹H NMR (400 MHz, CDCl₃) δ1.11 (t, J=7.2 Hz, 3H), 1.76-1.88 (m,2H), 2.02 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.80 (t,J=7.6 Hz, 2H), 3.19 (t, J=6.8 Hz, 2H), 4.93 (t, J=6.4 Hz, 2H), 6.32 (s,1H), 6.97 (s, 2H).

Example 1703-Mesityl-2,5-dimethyl-8-[2-(3-pyridyl)ethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0934] MS (ESI) m/z 410 MH⁺

Example 1718-(Dicyclopropylmethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0935] MS (ESI) m/z 399 MH⁺

Example 1723-Mesityl-2,5-dimethyl-8-phenethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0936] White Crystals

[0937] MS (ESI) m/z 409 MH⁺

Example 1733-Mesityl-2,5-dimethyl-8-(2-phenylpropyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0938] MS (ESI) m/z 423 MH⁺

Example 1742-(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylmethyl ether

[0939] White Crystals

[0940]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H),2.62 (s, 3H), 3.39 (s, 3H), 3.90 (t, J=5.2 Hz, 2H), 5.00 (t, J=5.2 Hz,2H), 6.52 (d, J=3.4 Hz, 1H), 6.89 (d, J=3.4 Hz, 1H), 6.97 (s, 2H).

Example 1753-(3-Mesityl-2,5-dimethyl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether hydrochloride

[0941] White Crystals

[0942]¹H NMR (400 MHz, DMSO-d₆) δ1.94 (s, 6H), 2.11-2.20 (m, 2H), 2.19(s, 3H), 2.32 (s, 3H), 2.69 (s, 3H), 3.19 (s, 3H), 3.39 (t, J=6.0 Hz,2H), 4.82 (t, J=7.0 Hz, 2H), 6.92 (d, J=3.3 Hz, 1H), 7.01 (s, 2H), 7.35(d, J=3.3 Hz, 1H).

Example 176 (diastereomer mixture)3-Mesityl-2,5-dimethyl-8-(2-methylcyclohexyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0943] Pale Yellow Oil

[0944]¹H NMR (400 MHz, DMSO-d₆) δ0.66-0.82 (d×2, J=6.6, 6.9 Hz, 3H),1.16-2.12 (m, 9H), 1.90-1.95 (s×2, 6H), 2.16-2.20 (s×2, 3H), 2.31 (s,3H), 2.65 (s, 3H), 5.50-5.75 (m, 1H), 6.84-6.98 (br d×2, J=3.0, 3.0 Hz,1H), 6.99 (s, 2H), 7.37-7.55 (br d×2, J=3.0, 3.0 Hz, 1H).

Example 1778-(1-Ethyl-1H-5-pyrazolyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0945] Brown Oil

[0946]¹H NMR (400 MHz, CDCl₃) δ1.35 (t, J=7.2 Hz, 3H), 1.98 (s, 6H),2.09 (s, 3H), 2.32 (s, 3H), 2.69 (s, 3H), 3.92 (q, J=7.2 Hz, 2H), 6.48(d, J=1.2 Hz, 1H), 6.73 (d, J=3.6 Hz, 1H), 6.82 (d, J=3.6 Hz, 1H), 6.95(s, 2H), 7.69 (d, J=1.2 Hz, 1H).

Example 1788-Isobutyl-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0947] Yellow Oil

[0948]¹H NMR(400 MHz, CDCl₃) δ0.97 (t, J=6.8 Hz, 6H), 1.08 (t, J=7.2 Hz,3H), 1.76-1.81 (m, 2H), 2.03 (s, 6H), 2.24 (s, 3H), 2.30-2.35 (m, 1H),2.33 (s,3H), 2.60 (s, 3H), 2.69 (t, J=8.0 Hz, 2H), 4.45-4.58 (m, 2H),6.27 (s, 1H), 6.96 (s, 2H).

Example 1798-(2-Ethylbutyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0949] Brown Oil

[0950]¹H-NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.08 (t, J=7.2Hz, 3H), 1.24-1.36 (m, 2H), 1.38-1.52 (m, 2H), 1.74-1.84 (m, 2H),1.96-2.04 (m, 1H), 2.03 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.60 (s,3H), 2.69 (t, J=7.6 Hz, 2H), 4.59-4.62 (m, 2H), 6.28 (s, 1H), 6.97 (s,2H).

Example 1803-Mesityl-2,5-dimethyl-8-(1-methylbutyl)-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0951] Brown Crystals

[0952]¹H-NMR (400 MHz, CDCl₃) δ0.92 (t, J=7.6 Hz, 3H), 1.12 (t, J=7.2Hz, 3H), 1.11-1.22 (m, 2H), 1.23-1.44 (m, 2H), 1.65 (d, J=6.8 Hz, 3H),1.81-1.87 (m, 2H), 2.02 (s, 3H), 2.03 (s, 3H), 2.24 (s, 3H), 2.33 (s,3H), 2.58 (s, 3H), 2.80-2.90 (m, 2H), 6.32 (s, 1H), 6.84-6.92 (m, 1H),6.97 (s, 2H).

Example 1818-(1-Benzylbutyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0953] Brown Amorphous

[0954] MS (ESI) m/z 451 MH⁺

Example 1823-Mesityl-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0955] White Crystals

[0956] MS (ESI) m/z 407 MH⁺

Example 1834-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine-3-yl]-3,5-dimethylphenylmethyl ether

[0957] White Crystals

[0958]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.2 Hz, 6H), 1.82-2.04 (m,4H), 2.05 (s, 6H), 2.24 (s, 3H), 2.63 (s, 3H), 3.83 (s, 3H), 5.97 (br s,1H), 6.59 (d, J=3.6 Hz, 1H), 6.71 (s, 2H), 6.86 (d, J=3.6 Hz, 1H).

Example 1848-(1-Ethyl-3-methylbutyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0959] Brown Oil

[0960]¹H NMR (400 MHz, CDCl₃) δ0.83 (t, J=7.2 Hz, 3H), 0.90 (d, J=6.8Hz, 3H), 0.95 (d, J=6.4 Hz, 3H), 1.32-1.40 (m, 1H), 1.70-2.00 (m, 4H),2.03 (s, 3H), 2.04 (s, 3H), 2.23 (s, 3H), 2.33 (s, 3H), 2.62 (s, 3H),6.10-6.20 (m, 1H), 6.59 (d, J=3.2 Hz, 1H), 6.85 (d, J=3.6 Hz, 1H), 6.97(s, 2H).

Example 1858-(2-Ethoxyethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0961] Yellow Oil

[0962]¹H NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.14 (t, J=6.8Hz, 3H), 1.74-1.83 (m, 2H), 2.02 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H),2.60 (s, 3H), 2.78 (t, J=7.6 Hz, 2H), 3.51 (q, J=6.8 Hz, 2H), 3.90 (t,J=6.0 Hz, 2H), 4.89 (t, J=5.6 Hz, 2H), 6.26 (s, 1H), 6.97 (s, 2H).

Example 1868-Cycloheptyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0963] White Crystals

[0964]¹H NMR (400 MHz, DMSO-d₆) δ1.57-1.88 (m, 8H), 1.94 (s, 6H),2.00-2.20 (m, 4H), 2.19 (s, 3H), 2.32 (s, 3H), 2.66 (s, 3H), 5.90 (br s,1H), 6.93 (br d, J=3.2 Hz, 1H), 7.00 (s, 2H), 7.52 (br d, J=3.2 Hz, 1H).

Example 1874-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine-3-yl]-3,5-dimethylphenylisopropyl ether

[0965] White Crystals

[0966]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.0 Hz, 6H), 1.36 (d, J=6.0Hz, 6H), 1.80-2.05 (m, 4H), 2.03 (s, 6H), 2.23 (s, 3H), 2.64 (s, 3H),4.50-4.62 (m, 1H), 6.59 (d, J=3.4 Hz, 1H), 6.69 (s, 2H), 6.86 (d, J=3.4Hz, 1H).

Example 1888-(1-Ethylpropyl)-2,5-dimethyl-3-(3-pyridyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinedihydrochloride

[0967] White Crystals

[0968]¹H NMR (400 MHz, DMSO-d₆) δ0.71 (t, J=7.4 Hz, 6H), 1.90-2.00 (m,4H), 2.71 (s, 3H), 2.75 (s, 3H), 5.80 (br s, 1H), 6.96 (d, J=3.5 Hz,1H), 7.49 (d, J=3.5 Hz, 1H), 8.14 (dd, J=8.4, 5.5 Hz, 1H), 8.77 (d,J=5.5 Hz, 1H), 9.01 (dd, J=8.4, 2.0 Hz, 1H), 9.40 (d, J=2.0 Hz, 1H).

Example 1898-Isobutyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0969] White Crystals

[0970]¹H NMR (400 MHz, DMSO-d₆) δ0.93 (d, J=6.8 Hz, 6H), 1.93 (s, 6H),2.17 (s, 3H), 2.22-2.32 (m, 1H), 2.31 (s, 3H), 2.64 (s, 3H), 4.58 (d,J=7.3 Hz, 2H), 6.85 (br d, J=3.0 Hz, 1H), 6.99 (s, 2H), 7.32 (br d,J=3.0 Hz, 1H).

Example 1903-Mesityl-8-(4-methoxybutyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0971] Yellow Oil

[0972]¹H NMR (400 MHz, CDCl₃) δ1.09 (t, J=7.6 Hz, 3H), 1.69-1.83 (m,4H), 1.91-2.00 (m, 2H), 2.03 (s, 6H), 2.25 (s, 3H), 2.33 (s, 3H), 2.59(s, 3H), 2.71 (t, J=7.6 Hz, 2H), 3.35 (s, 3H), 3.48 (t, J=6.4 Hz, 2H),4.76 (t, J=8.0 Hz, 2H), 6.26 (s, 1H), 6.97 (s, 2H).

Example 1918-Benzyl-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0973] White Amorphous

[0974]¹H NMR (400 MHz, CDCl₃) δ0.98 (t, J=7.6 Hz, 3H), 1.64-1.72 (m,2H), 2.03 (s, 6H), 2.19 (s, 3H), 2.33 (s, 3H), 2.53 (t, J=8.0 Hz, 2H),2.63 (s, 3H), 6.21 (s, 2H), 6.33 (s, 1H), 6.97 (s, 2H), 7.11 (d, J=6.8Hz, 2H), 7.24-7.33 (m, 3H).

Example 1928-(2-Furylmethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0975] White Amorphous

[0976]¹H NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.72-1.82 (m,2H), 2.03 (s, 6H), 2.27 (s, 3H), 2.33 (s, 3H), 2.59 (s, 3H), 2.81 (t,J=7.6 Hz, 2H) 6.09 (s, 2H), 6.28 (s, 1H), 6.30 (dd, J=2.8, 3.2 Hz, 1H),6.40 (dd, J=0.4, 2.8 Hz, 1H), 6.97 (s, 2H), 7.35 (dd, J=0.8, 5.6 Hz,1H).

Example 1934-(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)-1-butanol

[0977] Pale Yellow Oil

[0978]¹H NMR (400 MHz, CDCl₃) δ1.10 (t, J=7.6 Hz, 3H), 1.72-1.86 (m,4H), 2.02 (s, 6H), 2.04-2.12 (m, 2H), 2.27 (s, 3H), 2.33 (s, 3H), 2.60(s, 3H), 2.71 (s, 3H), 3.90 (dd, J=6.4, 12.0 Hz, 2H), 4.47 (t, J=6.8 Hz,1H), 4.67 (t, J=8.0 Hz, 2H), 6.29 (s, 1H), 6.97 (s, 2H).

Example 1943-Mesityl-2,5-dimethyl-7-propyl-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0979] Brown Oil

[0980]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.6 Hz, 3H), 1.58-1.68 (m,2H), 2.06 (s, 6H), 2.31 (s, 3H), 2.34 (s, 3H), 2.62 (t, J=7.6 Hz, 2H),2.66 (s, 3H), 6.27 (s, 1H), 6.98 (s, 2H), 11.58 (s, 1H).

Example 1953-(4-Bromo-2-methylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0981] White Crystals

[0982]¹H NMR (400 MHz, CDCl₃) δ0.82-0.94 (m, 6H), 1.80-2.05 (m, 4H),2.23 (s, 3H), 2.36 (s, 3H), 2.67 (s, 3H), 5.96 (br s, 1H), 6.62 (d,J=3.5 Hz, 1H), 6.88 (d, J=3.5 Hz, 1H), 7.18 (d, J=8.1 Hz, 1H), 7.38 (dd,J=8.1, 2.1 Hz, 1H), 7.48 (d, J=2.1 Hz, 1H).

Example 1963-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-6-methyl-2-pyridylmethylether

[0983] White Crystals

[0984]¹H NMR (400 MHz, CDCl₃) δ0.85 (t, J=7.3 Hz, 6H), 1.78-2.03 (m,4H), 2.41 (s, 3H), 2.51 (s, 3H), 2.66 (s, 3H), 3.97 (s, 3H), 5.97 (br s,1H), 6.59 (d, J=3.5 Hz, 1H), 6.85 (d, J=3.5 Hz, 1H), 6.86 (d, J=7.3 Hz,1H), 7.71 (d, J=7.3 Hz, 1H).

Example 197 3-Mesityl-2,5-dimethyl-8-(1-phenylpropyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0985] MS (ESI) m/z 423 MH⁺

Example 1988-Benzhydryl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0986] White Crystals

[0987] MS (ESI) m/z 471 MH⁺

Example 1998-(1,2-Diphenylethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[0988] Yellow Amorphous

[0989] MS (ESI) m/z 485 MH⁺

Example 2008-(2-Isopropoxyethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0990] Yellow Oil

[0991]¹H NMR (400 MHz, CDCl₃) δ1.06 (m, 3H), 1.10 (d, J=6.0 Hz, 6H),1.74-1.82 (m, 2H), 2.03 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.60 (s,3H), 2.79 (t, J=7.6 Hz, 2H), 3.57-3.63 (m, 1H), 3.89 (t, J=6.0 Hz, 2H),4.86 (t, J=6.0 Hz, 2H), 6.25 (s, 1H), 6.97 (s, 2H).

Example 2012-(3-Mesityl-2,5-dimethyl-7-propyl-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylpropylether

[0992] Yellow Oil

[0993]¹H NMR (400 MHz, CDCl₃) δ0.86 (t, J=7.6 Hz, 3H), 1.08 (t, J=7.6Hz, 3H), 1.48-1.58 (m, 2H), 1.74-1.83 (m, 2H), 2.03 (s, 6H), 2.23 (s,3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.78 (t, J=7.6 Hz, 2H), 3.40 (t, J=6.4Hz, 2H), 3.89 (t, J=6.4 Hz, 2H), 4.90 (t, J=5.6 Hz, 2H), 6.26 (s, 1H),6.97 (s, 2H).

Example 2025-[8-(1-Ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]-6-methyl2-pyridylmethyl ether

[0994] White Crystals

[0995]¹H NMR (400 MHz, CDCl₃) δ0.82-0.94 (m, 6H), 1.80-2.05 (m, 4H),2.35 (s, 3H), 2.38 (s, 3H), 2.67 (s, 3H), 3.97 (s, 3H), 5.96 (br s, 1H),6.61 (d, J=3.5 Hz, 1H), 6.66 (d, J=8.3 Hz, 1H), 6.87 (d, J=3.5 Hz, 1H),7.51 (d, J=8.3 Hz, 1H).

Example 2033-(7-Ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]propylmethyl ether

[0996] White Crystals

[0997]¹H NMR (400 MHz, CDCl₃) δ1.39 (t, J=7.6 Hz, 3H), 2.02 (s, 6H),2.16-2.24 (m, 2H), 2.33 (s, 3H), 2.60 (s, 3H), 2.78 (q, J=7.2 Hz, 2H),3.34 (s, 3H), 3.47 (t, J=6.4 Hz, 2H), 4.78 (t, J=6.8 Hz, 2H), 6.27 (s,1H), 6.96 (s, 2H).

Example 2043-Mesityl-8-[(1R)-3-methoxy-1-(methoxymethyl)propyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[0998] Yellow Oil

[0999]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.20-2.30 (m, 2H), 2.24 (s,3H), 2.33 (s, 3H), 2.63 (s, 3H), 3.17 (s, 3H), 3.23-3.42 (m, 2H), 3.89(s, 3H), 3.76-3.96 (m, 2H), 6.38-6.58 (m, 1H), 6.57 (d, J=3.6 Hz, 1H),6.97 (s, 2H), 7.03 (br s, 1H).

Example 2053-Mesityl-2,5-dimethyl-8-phenethyl-7-propyl-8H-cyclopenta[e]pyrazolo[1,5-a]pyrimdine

[1000] Yellow Oil

[1001]¹H NMR (400 MHz, CDCl₃) δ1.05 (t, J=7.6 Hz, 3H), 1.70-1.80 (m,2H), 2.05 (s, 6H), 2.30 (s, 3H), 2.34 (s, 3H), 2.56 (t, J=7.2 Hz, 2H),2.61 (s, 3H), 3.21 (t, J=7.6 Hz, 2H), 4.91 (t, J=7.6 Hz, 2H), 6.26 (s,1H), 6.98 (s, 2H), 7.21-7.27 (m, 1H), 7.28-7.34 (m, 4H).

Example 206N-(2-(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethyl)-N,N-dimethylamine

[1002] Yellow Oil

[1003]¹H NMR (400 MHz, CDCl₃) δ1.09 (t, J=7.2 Hz, 3H), 1.74-1.84 (m,2H), 2.03 (s, 6H), 2.24 (s, 3H), 2.33 (s, 3H), 2.45 (s, 6H), 2.59 (s,3H), 2.73 (t, J=7.2 Hz, 2H), 2.81 (t, J=7.6 Hz, 2H), 4.86 (t, J=7.6 Hz,2H), 6.27 (s, 1H), 6.97 (s, 2H).

Example 2073-Mesityl-8-(2-methoxyethyl)-7-(3-methoxypropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1004] Yellow Oil

[1005]¹H NMR (400 MHz, CDCl₃) δ1.95-2.06 (m, 2H), 2.03 (s, 6H), 2.23 (s,3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.89 (t, J=8.0 Hz, 2H), 3.35 (s, 3H),3.39 (s, 3H), 3.52 (t, J=6.0 Hz, 2H), 3.88 (t, J=6.0 Hz, 2H), 4.90 (t,J=5.6 Hz, 2H), 6.27 (s, 1H), 6.97 (s, 2H).

Example 2087-(3-(Benzyloxy)propyl)-3-mesityl-8-(2-methoxyethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1006] Yellow Oil

[1007]¹H NMR (400 MHz, CDCl₃) δ1.72-2.20 (m, 2H), 1.95 (s, 6H), 2.16 (s,3H), 2.26 (s, 3H), 2.54 (s, 3H), 2.85 (t, J=7.2 Hz, 2H), 3.27 (s, 3H),3.55 (t, J=6.0 Hz, 2H), 3.80 (t, J=5.6 Hz, 2H), 4.49 (s, 2H), 4.82 (t,J=6.0 Hz, 2H), 6.17 (s, 1H), 6.90 (s, 2H), 7.19-7.23 (m, 1H), 7.25-7.31(m, 4H).

Example 2097-Benzyl-8-butyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1008] MS (ESI) m/z 451 MH⁺

Example 2107-Benzyl-3-mesityl-2,5,8-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1009] Pale Yellow Amorphous

[1010]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.25 (s, 3H), 2.33 (s, 3H),2.59 (s, 3H), 4.12 (s, 2H), 4.23 (s, 3H), 6.31 (s, 1H), 6.97 (s, 2H),7.21-7.36 (m, 5H).

[1011] MS (ESI) m/z 409 MH⁺

Example 2117-Ethyl-8-(2-isopoxyethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1012]¹H NMR (400 MHz, CDCl₃) δ1.10 (d, J=6.0 Hz, 6H), 1.38 (t, J=7.6Hz, 3H), 2.03 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.84(q, J=7.6 Hz, 2H), 3.59 (hept., J=6.0 Hz, 1H), 3.89 (t, J=6.0 Hz, 2H),4.86 (t, J=6.0 Hz, 2H), 6.26 (s, 1H), 6.97 (s, 2H).

[1013] MS (ESI) m/z 419 MH⁺

Example 2123-Mesityl-8-(2-(2-methoxyethoxy)ethyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1014] Reddish Brown Oil

[1015]¹H NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.74-1.82 (m,2H), 2.02 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.77 (t,J=6.8 Hz, 2H), 3.34 (s, 3H), 3.46-3.48 (m, 2H), 3.63-3.65 (m, 2H), 3.97(t, J=6.0 Hz, 2H), 4.91 (t, J=5.6 Hz, 2H), 6.26 (s, 1H), 6.96 (s, 2H).

Example 213 2-Bromoethyl(2-(3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimridin-8-yl)ethyl)ether

[1016] Yellow Oil

[1017]¹H NMR (400 MHz, CDCl₃) δ1.09 (t, J=7.2 Hz, 3H), 1.74-1.83 (m,2H), 2.03 (s, 6H), 2.23 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.79 (t,J=7.2 Hz, 2H), 3.40 (t, J=6.0 Hz, 2H), 3.80 (t, J=6.0 Hz, 2H), 4.00 (t,J=5.6 Hz, 2H), 4.91 (t, J=5.6 Hz, 2H), 6.27 (s, 1H), 6.97 (s, 2H).

Example 214(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methylmethyl ether

[1018] Pale Yellow Oil

[1019]¹H NMR (400 MHz, CDCl₃) δ2.02 (s, 6H), 2.27 (s, 3H), 2.33 (s, 3H),2.65 (s, 3H), 3.46 (s, 3H), 6.17 (s, 2H), 6.61 (d, J=3.6 Hz, 1H), 6.94(d, J=3.2 Hz, 1H), 6.97 (s, 2H).

Example 2158-(1-Ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethyl-3-pyridyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1020] White Crystals

[1021]¹H NMR (400 MHz, CDCl₃) δ0.85-0.92 (m, 6H), 1.83-2.05 (m, 4H),2.06 (s, 3H), 2.24 (s, 3H), 2.31 (s, 3H), 2.55 (s, 3H), 2.64 (s, 3H),5.95 (br s, 1H), 6.62 (d, J=3.5 Hz, 1H), 6.88 (d, J=3.5 Hz, 1H), 6.97(s, 1H).

Example 2164-[8-(1-Ethylbutyl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-3,5-dimethylphenylmethyl ether

[1022] White Crystals

[1023]¹H NMR (400 MHz, CDCl₃) δ0.87 (t, J=7.6 Hz, 3H), 0.91 (t, J=7.4Hz, 3H), 1.13-1.40 (m, 2H), 1.82-2.03 (m, 4H), 2.05 (s, 6H), 2.23 (s,3H), 2.63 (s, 3H), 3.83 (s, 3H), 6.06 (br s, 1H), 6.59 (d, J=3.6 Hz,1H), 6.71 (s, 2H), 6.86 (d, J=3.6 Hz, 1H).

Example 2173-(4-Methoxy-2,6-dimethylphenyl)-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1024] White Crystals

[1025]¹H NMR (400 MHz, CDCl₃) δ0.95 (t, J=7.4 Hz, 3H), 1.95-2.10 (m,2H), 2.03 (s, 3H), 2.05 (s, 3H), 2.23 (s, 3H), 2.63 (s, 3H), 3.38 (s,3H), 3.74-3.79 (m, 1H), 3.80-3.90 (m, 1H), 3.82 (s, 3H), 6.19 (br s,1H), 6.57 (d, J=3.6 Hz, 1H), 6.71 (s, 2H), 7.00 (d, J=3.6 Hz, 1H).

Example 2183-(4-Ethoxy-2,6-dimethylphenyl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1026] Pale Yellow Crystals

[1027]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.3 Hz, 6H), 1.43 (t, J=7.0Hz, 3H), 1.82-2.05 (m, 4H), 2.04 (s, 6H), 2.23 (s, 3H), 2.63 (s, 3H),4.05 (q, J=7.0 Hz, 2H), 5.96 (br s, 1H), 6.59 (d, J=3.5 Hz, 1H), 6.70(s, 2H), 6.85 (d, J=3.5 Hz, 1H).

Example 2193-(Mesityl-2,5-dimethyl-8-[(1S)-1-phenylethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1028] MS (FAB) m/z 409 MH⁺

Example 2203-Mesityl-8-(3-methoxybenzyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1029] MS (FAB) m/z 425 MH⁺

Example 2213-Mesityl-8-(4-methoxybenzyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1030] MS (FAB)m/z 425 MH⁺

Example 2223-Mesityl-2,5-dimethyl-8-(2-methylbenzyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1031] MS (FAB) m/z 409 MH⁺

Example 2233-Mesityl-2,5-dimethyl-8-(3-methylbenzyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1032] MS (FAB) m/z 409 MH⁺

Example 2243-Mesityl-2,5-dimethyl-8-[(1R)-1-phenylethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1033] MS (FAB) m/z 409 MH⁺

Example 225 Ethyl4-(3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)butanone

[1034] MS (FAB) m/z 419 MH⁺

Example 2263-Mesityl-2,5-dimethyl-8-[2-(methylsulfanil)ethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1035] MS (ESI) m/z 379 MH⁺

Example 2273-Mesityl-2,5-dimethyl-8-(1,2,2-trimethylpropyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1036] MS (FAB) m/z 389 MH⁺

Example 228(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl methyl ether

[1037] Yellow Oil

[1038]¹H NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.75-1.84 (m,2H), 2.02 (s, 6H), 2.26 (s, 3H), 2.33 (s, 3H), 2.62 (s, 3H), 2.79 (t,J=7.2 Hz, 2H), 3.43 (s, 3H), 6.27 (s, 2H), 6.34 (s, 1H), 6.97 (s, 2H).

Example 2293-Mesityl-2,5-dimethyl-8-pentyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin

[1039] MS (ESI) m/z 417 MH⁺

Example 2303-(8-Ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-7-yl)propylmethyl ether

[1040] Yellow Oil

[1041]¹H NMR (400 MHz, CDCl₃) δ1.51 (t, J=7.2 Hz, 3H), 2.00-2.08 (m,2H), 2.03 (s, 6H), 2.26 (s, 3H), 2.33 (s, 3H), 2.60 (s, 3H), 2.84 (t,J=7.6 Hz, 2H), 3.40 (s, 3H), 3.52 (t, J=6.0 Hz, 2H), 4.82 (dd, J=7.2,7.2 Hz, 2H), 6.28 (s, 1H), 6.97 (s, 2H).

Example 2313-(6-Bromo-1,3-benzodioxol-5-yl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1042] White Crystals

[1043]¹H NMR (400 MHz, CDCl₃) δ0.85 (t, J=7.3 Hz, 3H), 0.88 (t, J=7.3Hz, 3H), 1.80-2.03 (m, 4H), 2.39 (s, 3H), 2.68 (s, 3H), 5.95 (br s, 1H),6.02 (d, J=7.6 Hz, 1H), 6.02 (d, J=7.6 Hz, 1H), 6.61 (d, J=3.5 Hz, 1H),6.86 (d, J=3.5 Hz, 1H), 6.89 (s, 1H), 7.16 (s, 1H).

Example 2328-Butyl-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1044]¹H NMR (400 MHz, CDCl₃) δ1.03 (t, J=7.2 Hz, 3H), 1.51 (qt, J=7.2Hz, 7.6 Hz, 2H), 1.88-1.98 (m, 2H), 2.03 (s, 6H), 2.25 (s, 3H), 2.33 (s,3H), 2.60 (s, 3H), 3.36 (s, 3H), 4.58 (s, 2H), 4.78 (t, J=7.2 Hz, 2H),6.52 (s, 1H), 6.97 (s, 2H).

[1045] MS (ESI) m/z 405 MH⁺

Example 2337,8-Dibutyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1046] Pale Yellow Crystals

[1047] MS (ESI) m/z 417 MH⁺

Example 2343-Mesityl-2,5-dimethyl-8-propyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1048] MS (ESI) m/z 385 MH⁺

Example 2358-Butyl-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1049] MS (ESI) m/z 399 MH⁺

Example 2363-Mesityl-2,5-dimethyl-8-pentyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1050] MS (ESI) m/z 413 MH⁺

Example 2378-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1051] MS (ESI) m/z 413 MH⁺

Example 2388-(2-Ethylbutyl)-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1052] MS (ESI) m/z 427 MH⁺

Example 2398-Isopentyl-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1053] MS (ESI) m/z 413 MH⁺

Example 2408-Allyl-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1054] MS (ESI) m/z 383 MH⁺

Example 2418-(2-Ethoxyethyl)-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1055] MS (ESI) m/z 415 MH⁺

Example 2422-[3-Mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]ethylpropylether

[1056] MS (ESI) m/z 429 MH⁺

Example 2438-(2-Isopropoxyethyl)-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1057] MS (ESI) m/z 429 MH⁺

Example 2443-[3-Mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]propylmethyl ether

[1058] MS (ESI) m/z 415 MH⁺

Example 2452-[(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl]phenylmethyl ether

[1059] MS (ESI) m/z 467 MH⁺

Example 2463-[(3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl]phenylmethyl ether

[1060] MS (ESI) m/z 467 MH⁺

Example 2473-Mesityl-8-(4-methoxybenzyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1061] MS (ESI) m/z 467 MH⁺

Example 2488-(1,3-Benzodioxol-5-ylmethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1062] MS (ESI) m/z 481 MH⁺

Example 2498-(3-Ethoxypropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1063] MS (ESI) m/z 433 MH⁺

Example 2508-(3-Isopropoxypropyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1064] MS (ESI) m/z 447 MH⁺

Example 2513-Mesityl-2,5-dimethyl-7,8-dipropyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1065] MS (ESI) m/z 389 MH⁺

Example 2522-[3-Mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl]ethylmethyl ether

[1066] MS (ESI) m/z 401 MH⁺

Example 2537-Butyl-8-(2-isopropoxyethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1067] MS (FAB) m/z 447 MH⁺

Example 2548-Benzyl-7-butyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1068] MS (FAB) m/z 451 MH⁺

Example 2557-Butyl-8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1069] MS (FAB) m/z 431 MH⁺

Example 2567-Butyl-3-mesityl-2,5-dimethyl-8-[(1S)-1-phenylethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidine

[1070] MS (FAB) m/z 465 MH⁺

Example 2577-Butyl-3-mesityl-8-(3-methoxypropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1071] MS (FAB)m/z 433 MH⁺

Example 2588-(2-Isopropoxyethyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1072] MS (FAB)m/z 435 MH⁺

Example 2598-Benzyl-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1073] MS (FAB) m/z 439 MH⁺

Example 2603-Mesityl-7-(methoxymethyl)-2,5-dimethyl-8-[(1S)-1-phenylethyl]-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1074] MS (FAB) m/z 453 MH⁺

Example 2617-Butyl-3-mesityl-8-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1075] MS (FAB) m/z 419 MH⁺

Example 2628-(2-Ethoxyethyl)-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1076] MS (ESI) m/z 391 MH⁺

Example 2632-(3-Mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylpropyl ether

[1077] MS (ESI) m/z 405 MH⁺

Example 2648-(2-Isopropoxyethyl)-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1078] MS (ESI) m/z 405 MH⁺

Example 2653-(3-Mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether

[1079] MS (ESI) m/z 391 MH⁺

Example 2668-(3-Ethoxypropyl)-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1080] MS (ESI) m/z 405 MH⁺

Example 2673-(3-Mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylpropyl ether

[1081] MS (ESI) m/z 419 MH⁺

Example 2688-(3-Isopropoxypropyl)-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1082] MS (ESI) m/z 419 MH⁺

Example 2698-Benzyl-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1083] MS (ESI) m/z 409 MH⁺

Example 2703-Mesityl-2,5-dimethyl-8-(3-propoxypropyl)-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1084] MS (ESI) m/z 447 MH⁺

Example 2714-((7-Allyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl)phenylmethyl ether

[1085] Yellow Oil

[1086]¹H NMR (400 MHz, CDCl₃) δ2.04 (s, 6H), 2.21 (s, 3H), 2.33 (s, 3H),2.62 (s, 3H), 3.34 (d, J=6.0 Hz, 2H), 3.78 (s, 3H), 5.11 (dd, J=1.2,18.8 Hz, 1H), 5.18 (dd, J=1.2, 10.4 Hz, 1H), 5.38-6.00 (m, 1H), 6.13 (s,2H), 6.34 (s, 1H), 6.85 (d, J=8.4 Hz, 2H), 6.97 (s, 2H), 7.07 (d, J=8.8Hz, 2H).

Example 2728-Benzyl-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1087] MS (ESI) m/z 433 MH⁺

Example 2733-Mesityl-8-(4-methoxybenzyl)-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1088] MS (ESI) m/z 463 MH⁺

Example 2748-(1,3-Benzodioxol-5-ylmethyl)-3-mesityl-2,5-dimethyl-7-(1-propynyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1089] MS (ESI) m/z 477 MH⁺

Example 2758-Benzyl-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1090] MS (ESI) m/z 409 MH⁺

Example 2763-Mesityl-8-(4-methoxybenzyl)-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1091] MS (ESI) m/z 439 MH⁺

Example 2778-(1-Benzodioxol-5-ylmethyl)-3-mesityl-2,5,7-trimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1092] MS (ESI) m/z 453 MH⁺

Example 2788-Butyl-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1093] MS (ESI) m/z 403 MH⁺

Example 2798-Allyl-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1094] MS (ESI) m/z 387 MH⁺

Example 2808-(2-Ethoxyethyl)-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1095] MS (ESI) m/z 419 MH⁺

Example 2818-(2-Isopropoxyethyl)-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]primidine

[1096] MS (ESI) m/z 433 MH⁺

Example 2823-(7-Isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether

[1097] MS (ESI) m/z 419 MH⁺

Example 2838-Benzyl-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1098] MS (ESI) m/z 437 MH⁺

Example 2844-((7-Isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl)phenylmethyl ether

[1099] MS (ESI) m/z 467 MH⁺

Example 2858-(1,3-Benzodioxol-5-ylmethyl)-7-isopropyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1100] MS (ESI) m/z 481 MH⁺

Example 2867-Allyl-8-butyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1101] MS (ESI) m/z 401 MH⁺

Example 2877,8-Diallyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1102] MS (ESI) m/z 385 MH⁺

Example 2882-(7-Allyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylmethyl ether

[1103] MS (ESI) m/z 403 MH⁺

Example 2892-(7-Allyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylethyl ether

[1104] MS (ESI) m/z 417 MH⁺

Example 2902-(7-Allyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylisopropyl ether

[1105] MS (ESI) m/z 431 MH⁺

Example 2913-(7-Allyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)propylmethyl ether

[1106] MS (ESI) m/z 417 MH⁺

Example 2927-Allyl-8-benzyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1107] MS (ESI) m/z 435 MH⁺

Example 2937-Allyl-8-(1,3-benzodioxol-5-ylmethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1108] MS (ESI) m/z 479 MH⁺

Example 2948-(3-Isopropoxypropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1109] Yellow Oil

[1110] MS (ESI) m/z 405 MH⁺

Example 2956,7-Dibromo-8-(3-isopropoxypropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1111] MS (ESI) m/z 563 MH⁺

Example 2967-Bromo-8-(3-isoproploxypropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1112] MS (ESI) m/z 483 MH⁺

Example 2978-(2-Isopropoxyethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1113] Pale Brown Crystals

[1114] MS (ESI) m/z 391 MH⁺

Example 2986-Bromo-8-(2-isopropoxyethyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1115]¹H NMR (400 MHz, CDCl₃) δ1.09 (d, J=6.0 Hz, 6H), 2.02 (s, 6H),2.23 (s, 3H), 2.34 (s, 3H), 2.85 (s, 3H), 3.36 (s, 3H), 3.58 (hept.,J=6.4 Hz, 1H), 3.90 (t, J=5.6 Hz, 2H), 4.79 (s, 2H), 5.06 (t, J=5.6 Hz,2H), 6.70 (s,2H).

Example 2993-Mesityl-7-(methoxymethyl)-2,5-dimethyl-8-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1116] MS (FAB) m/z 391 MH⁺

Example 3003-Mesityl-7-(methoxymethyl)-2,5-dimethyl-8-pentyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1117] MS (FAB) m/z 419 MH⁺

Example 3018-(Cyclopropylmethyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1118] MS (FAB) m/z 403 MH⁺

Example 3023-Mesityl-8-(2-methoxyethyl)-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1119] MS (FAB) m/z 407 MH⁺

Example 3038-(2-Ethoxyethyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1120] MS (FAB) m/z 421 MH⁺

Example 3043-Mesityl-7-(methoxymethyl)-2,5-dimethyl-8-(2-propoxyethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1121] MS (FAB) m/z 435 MH⁺

Example 3053-Mesityl-7-(methoxymethyl)-8-(3-methoxypropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1122] MS (FAB) m/z 421 MH⁺

Example 3068-(3-Ethoxypropyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1123] MS (FAB) m/z 435 MH⁺

Example 3078-(3-Isopropxypropyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1124] MS (FAB) m/z 449 MH⁺

Example 3083-Mesityl-8-(2-methoxybenzyl)-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1125] MS (FAB) m/z 469 MH⁺

Example 3093-Mesityl-8-(3-methoxybenzyl)-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1126] MS (FAB) m/z 469 MH⁺

Example 3103-Mesityl-8-(4-methoxybenzyl)-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1127] MS (FAB) m/z 469 MH⁺

Example 3118-(1,3-Benzodioxol-5-ylmethyl)-3-mesityl-7-(methoxymethyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1128] MS (FAB) m/z 483 MH⁺

Example 3127-Butyl-8-(2-ethoxyethyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1129] MS (FAB) m/z 433 MH⁺

Example 3137-Butyl-3-mesityl-8-(4-methoxybenzyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1130] MS (FAB) m/z 481 MH⁺

Example 3144-[(3-Mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl]phenyl

[1131] White Crystals

[1132] MS (ESI) m/z 411 MH⁺

Example 3158-(4-Isopropoxybenzyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidinehydrochloride

[1133] MS (ESI) m/z 453 MH⁺

Example 3164-(8-Butyl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)-3,5-dimethylphenylmethyl ether

[1134] MS (ESI) m/z 419 MH⁺

Example 3178-(2-Ethoxyethyl)-3-(4-methoxy-2,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1135] MS (ESI) m/z 435 MH⁺

Example 3188-(2-Isopropoxyethyl)-3-(4-methoxy-2,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1136] MS (ESI) m/z 449 MH⁺

Example 3193-(4-Methoxy-2,6-dimethylphenyl)-8-(3-methoxypropyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1137] MS (ESI) m/z 434 MH⁺

Example 3208-(4-Methoxybenzyl)-3-(4-methoxy-2,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1138] MS (ESI) m/z 483 MH⁺

Example 3213-(2-Bromo-4,6-dimethylphenyl)-8-butyl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1139] MS (ESI) m/z 467 MH⁺

Example 322 2-(3-(2-Bromo-4,6-dimethylpheny)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethyl methylether

[1140] MS (ESI) m/z 469 MH⁺

Example 3232-(3-(2-Bromo)-4,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylethyl ether

[1141] MS (ESI) m/z 483 MH⁺

Example 3242-(3-(2-Bromo-4,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylisopropyl ether

[1142] MS (ESI) m/z 497 MH⁺

Example 3253-(2-Bromo-4,6-dimethylphenyl)-8-(3-methoxypropyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1143] MS (ESI) m/z 483 MH⁺

Example 3263-(2-Bromo-4,6-dimethylphenyl)-8-(4-methoxybenzyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-]pyrimidine

[1144] MS (ESI) m/z 531 MH⁺

Example 3278-(Cyclohexylmethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1145] MS (ESI) m/z 443 MH⁺

Example 3288-Cyclohexyl-3-mesityl-2,5-dimethly-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1146] MS (ESI) m/z 429 MH⁺

Example 3298-(Dicyclopropylmethyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1147] MS (ESI) m/z 441 MH⁺

Example 3304-((3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl)-1-benzenesulfonamide

[1148] MS (ESI) m/z 516 MW⁺

Example 3313-Mesityl-2,5-dimethyl-7-propyl-8-(2-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1149] MS (ESI) m/z 438 MH⁺

Example 3323-Mesityl-2,5-dimethyl-7-propyl-8-(3-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1150] MS (ESI) m/z 438 MH⁺

Example 3333-Mesityl-2,5-dimethyl-7-propyl-8-(4-pyridylmethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1151] MS (ESI) m/z 438 MH⁺

Example 3347-Ethyl-8-(3-isopropoxypropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1152] MS (FAB) m/z 433 MH⁺

Example 3357-Ethyl-3-mesityl-8-(4-methoxybenzyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1153] MS (ESI) m/z 453 MH⁺

Example 3368-(2-Ethoxyethyl)-7-ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1154] Pale Yellow Crystals

[1155] MS (ESI) m/z 405 MH⁺

Example 3377-Ethyl-3-mesityl-2,5-dimethyl-8-(2-propoxyethyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1156] MS (ESI) m/z 419 MH⁺

Example 3388-(4-Chlorobenzyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1157] MS (ESI) m/z 471 MH⁺

Example 3398-(4-Fulorobenzyl)-3-mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1158] MS (ESI) m/z 455 MH⁺

Example 3403-Mesityl-2,5-dimethyl-7-propyl-8-(4-(trifuluoromethyl)benzyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1159] MS (ESI) m/z 505 MH⁺

Example 3413-Mesityl-2,5-dimethyl-7-propyl-8-(4-(trifuluoromethyl)benzyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1160] MS (ESI) m/z 521 MH⁺

Example 342N-(4-((3-Mesityl-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1161] MS (ESI) m/z 480 MH⁺

Example 3433-Mesityl-2,5-dimethyl-8-(4-methylbenzyl)-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1162] MS (ESI) m/z 451 MH⁺

Example 3443-(4-Methoxy-2,5-dimethylphenyl)-8-(2-methoxyethyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1163] MS (ESI) m/z 421 MH⁺

Example 3457-Ethyl-3-mesityl-8-[(6-methoxy-3-pyridyl)methyl]-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1164] Yellow Amorphous

[1165] MS (ESI) m/z 454 MH⁺

Example 3465-[(7-Ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl]-1,2-dihydro-2-pyridinone

[1166] White Crystals

[1167] MS (ESI) m/z 440 MH⁺

Example 3475-[(7-Ethyl-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)methyl]-1-methyl-1,2-dihydro-2-pyridinone

[1168] White Crystals

[1169] MS (ESI) m/z 454 MH⁺

Example 3482-(3-(4-Bromo-2,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-8-yl)ethylmethyl ether

[1170] Yellow Oil

[1171]¹H-NMR (400 MHz, CDCl₃) δ1.08 (t, J=7.2 Hz, 3H), 1.75-1.82 (m,2H), 2.03 (s, 6H), 2.21 (s, 3H), 2.60 (s, 3H), 2.77 (t, J=8.0 Hz, 2H),3.36 (s, 3H), 3.87 (t, J=5.6 Hz, 2H), 4.88 (t, J=5.6 Hz, 2H), 6.27 (s,1H), 7.29 (s, 2H).

Example 3492-(3-(4-Bromo-2,6-dimethylphenyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-pyrimidin-8-yl)ethylisopropyl ether

[1172] Yellow Oil

[1173]¹H-NMR (400 MHz, CDCl₃) δ1.01-1.03 (m, 3H), 1.03 (d, J=6.4 Hz,6H), 1.69-1.75(m, 2H), 1.97 (s, 6H), 2.14 (s, 3H), 2.54 (s, 3H), 2.72(s, 2H), 3.50-3.55 (m, 1H), 3.81 (t, J=6.0 Hz, 2H), 4.78 (t, J=6.0 Hz,2H), 6.20 (s, 1H), 7.22 (s, 2H).

Example 3503-(4-Bromo-2,6-dimethylphenyl)-8-(4-methoxybenzyl)-2,5-dimethyl-7-propyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1174] MS (ESI) m/z 533 MH⁺

Example 3513-Benzo[b]furan-2-yl-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1175] A solution of3-bromo-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(300 mg, 0.89 mmol), benzo[b]furan-2-yl(tributyl)tin (0.72 g, 1.78 mmol)and Pd(PPh₃)₄ (103 mg, 0.90 mmol) in N,N-dimethylformamide (15 mL) wasstirred at 120° C. for one day. Ethyl acetate and water were addedthereto, followed by filtering through Celite. The organic layer of thefiltrate was washed with brine, dried over anhydrous magnesium sulfateand evaporated. The residue was purified by silica gel columnchromatography (0-5% ethyl acetate/hexane), to give the title compound(111 mg) as white crystals.

[1176]¹H-NMR (400 MHz, CDCl₃) δ0.92 (t, J=7.2 Hz, 6H), 1.54-1.72 (m,4H), 2.43 (s, 3H), 2.76 (s, 3H), 3.13 (t, J=9.2 Hz, 2H), 3.69 (t, J=9.2Hz, 2H), 5.58-5.68 (m, 1H), 7.14-7.20 (m, 2H), 7.27 (d, J=0.8 Hz, 1H),7.46-7.50 (m, 1H), 7.53-7.56 (m, 1H).

Example 3523-(3-Bromobenzo[b]furan-2-yl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1177] Bromine (1.0 M solution in carbon tetrachloride 0.3 mL, 0.30mmol) was added to a solution of3-benzo[b]furan-2-yl-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(50 mg, 0.13 mmol) in N,N-dimethylformamide (0.3 mL) at 0° C., followedby stirring for one hour. Hypo water was added thereto, and the mixturewas diluted with ethyl acetate, washed with an aqueous saturatedsolution of ammonium chloride and brine, dried over anhydrous magnesiumsulfate and evaporated. The residue was purified by silica gel columnchromatography (10% ethyl acetate/hexane), to give the title compound(57 mg) as white crystals.

[1178]¹H-NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.2 Hz, 6H), 1.54-1.72 (m,4H), 2.36 (s, 3H), 2.49 (s, 3H), 3.12 (t, J=9.2 Hz, 2H), 3.70 (t, J=9.2Hz, 2H), 5.60-5.66 (m, 1H), 7.27-7.31 (m, 2H), 7.48-7.54 (m, 2H).

Example 3533-(3-Bromobenzo[b]furan-2-yl)-8-(1-ethylpropyl)-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1179] DDQ (33 mg, 0.15 mmol) was added to a solution of3-(3-bromobenzo[b]furan-2-yl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(60 mg, 0.13 mmol) in methylene chloride (10 mL) at room temperature,followed by stirring for one hour. After evaporating, the residue waspurified by silica gel column chromatography (10% ethyl acetate/hexane),to give the title compound (40 mg) as a reddish brown oil.

[1180]¹H-NMR (400 MHz, CDCl₃) δ0.85 (t, J=7.2 Hz, 6H), 1.78-2.04 (m,4H), 2.59 (s, 3H), 2.74 (s, 3H), 5.90-6.00 (m, 1H), 6.65 (d, J=3.2 Hz,1H), 6.91 (d, J=3.2 Hz, 1H), 7.27-7.36 (m, 2H), 7.50-7.59 (m, 2H).

Example 3548-(1-Ethylpropyl)-3-(1H-2-indolyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1181] A solution of2-2-[8-(1-ethynylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-1-ethynylaniline(540 mg, 1.45 mmol) and copper iodide (551 mg, 2.89 mmol) inN,N-dimethylformamide (10 mL) was stirred at 120° C. for one day. Afterfiltering through Celite, the filtrate was evaporated. The residue waspurified by dry pack silica gel column chromatography (30% ethylacetate/hexane), to give the title compound (15 mg) as pale yellowcrystals.

[1182]¹H-NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.55-1.70 (m,4H), 2.44 (s, 3H), 2.68 (s, 3H), 3.13 (t, J=9.2 Hz, 2H), 3.70 (t, J=9.2Hz, 2H), 5.58-5.70 (m, 1H), 6.55 (s, 1H), 7.06 (t, J=7.6 Hz, 1H), 7.11(t, J=7.6 Hz, 1H), 7.45 (d, J=7.6 Hz, 1H), 7.59 (d, J=7.6 Hz, 1H), 11.04(s, 1H).

Example 3553-(1H-Benzo[d]imidazol-2-yl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1183] DDQ (79 mg, 0.35 mmol) was added to a solution of8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-carbaldehyde(100 mg, 0.35 mmol) and 1,2-phenylenediamine (40 mg, 0.37 mmol) inacetonitrile (1 mL) at room temperature and the mixture was stirred forone day. Further, a 0.5N aqueous solution of sodium hydroxide was addedthereto, followed by stirring for five hours. The mixture was extractedwith ethyl acetate, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by dry pack silica gel columnchromatography (50% ethyl acetate/hexane), to give the title compound(23 mg) as pale yellow crystals.

[1184]¹H-NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.54-1.74 (m,4H), 2.45 (s, 3H), 2.93 (s, 3H), 3.15 (t, J=9.2 Hz, 2H), 3.73 (t, J=9.2Hz, 2H), 5.59-5.67 (m,1H), 7.15-7.22 (m, 2H), 7.49 (dd, J=7.2 Hz, 3.0Hz, 1H), 7.78 (d, J=7.2 Hz, 1H), 11.68 (s, 1H).

Example 3568-(1-Ethylpropyl)-2,5-dimethyl-3-(1-methyl-1H-benzo[d]imidazol-2-yl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1185] According to the method described in the above Example 354, thetitle compound (65 mg) was obtained as pale yellowish brown crystalsfrom8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-carbaldehyde(100 mg, 0.35 mmol).

[1186]¹H-NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.54-1.72 (m,4H), 2.32 (s, 3H), 2.59 (s, 3H), 3.12 (t, J=9.2 Hz, 2H), 3.71 (t, J=9.2Hz, 2H), 3.84 (s, 3H), 5.62-5.71 (m, 1H), 7.21-7.28 (m, 2H), 7.35-7.40(m, ,1H), 7.74-7.79 (m, 1H).

Example 3578-(1-Ethylpropyl)-2,5-dimethyl-3-(4-methyl-1H-benzo[d]imidazol-2-yl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1187] According to the method described in the above Example 354, thetitle compound (50 mg) was obtained as pale yellowish brown crystalsfrom8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-carbaldehyde(200 mg, 0.70 mmol).

[1188]¹H-NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6 Hz, 6H33 ½), 0.94(t, J=7.6 Hz, 6H×½), 1.54-1.75 (m, 4H), 2.44 (s, 3H), 2.60 (s, 3H×½),2.72 (s, 3H×½), 2.93 (s, 3H×½), 2.96 (s, 3H×½), 3.14 (t, J=9.2 Hz,2H×½), 3.15 (t, J=9.2 Hz, 2H×½), 3.72 (t, J=9.2 Hz, 2H×½), 3.73 (t,J=9.2 Hz, 2H×½), 5.58-5.67 (m, 1H), 6.96-7.15 (m, 2H), 7.32 (d, J=8.0Hz, 1H×½), 7.63 (d, J=8.0 Hz, 1H×½), 11.50 (s, 1H×½), 11.78 (s, 1H×½).

Example 3582-[8-(1-Ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidin-3-yl]-1H-benzo[d]imidazol-1-ylmethyl sulfone

[1189] Methanesulfonyl chloride (12 mL, 0.16 mmol) was added to asoltution of3-(1H-benzo[d]imidazol-2-yl)-8-(1-ethylpropyl)-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine(50 mg, 0.13 mmol) in pyridine (0.5 mL) at room temperature and themixture was stirred for one hour. Water was added thereto, and themixture was extracted with ethyl acetate, washed with brine, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (50% ethyl acetate/hexane), to give thetitle compound (48 mg) as pale yellow crystals.

[1190]¹H-NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.54-1.72 (m,4H), 2.24 (s, 3H), 2.49 (s, 3H), 3.09 (t, J=9.2 Hz, 2H), 3.69 (t, J=9.2Hz, 2H), 3.77 (s, 3H), 5.60-5.68 (m, 1H), 7.36-7.41 (m, 2H), 7.77-7.82(m, 1H), 7.89-7.94 (m, 1H).

Example 3596-Mesityl-1,3,4,7-tetramethyl-2,3-dihydro-1H-pyrazolo[5,1-b]purin-2-one

[1191] Hydrazine monohydrate (5 mL) was added to a solution of ethyl7-amino-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(809 mg, 2.30 mmol) in ethanol (30 mL), followed by heating under refluxfor eight hours. The reaction mixture was evaporated as it was, to givea crude compound. A 10% aqueous solution of hydrogen chloride was addedto a solution of the crude compound in ethanol (25 mL) underice-cooling, and a solution of sodium nitrite (177 mg, 2.53 mmol) inwater (10 mL) was gradually added dropwise. After one hour, atemperature was raised to room temperature and the mixture was stirredfor five hours. The reaction mixture was evaporated as it was, water wasadded, and the resulting solid was dried, to give a crude compound (571mg). Sodium hydride (27 mg, 0.66 mmol) was added to a solution of thecrude compound (107 mg, 0.33 mmol) in N,N-dimethylformamide (5 mL) atroom temperature. After 30 minutes, methyl iodide (0.052 mL, 0.83 mmol)was added, followed by stirring at the same temperature for one hour.Water was added under ice-cooling, followed by extracting with ether.The organic layer was washed with brine, dried over anhydrous magnesiumsulfate and evaporated. The residue was purified by silica gel columnchromatography (25% ethyl acetate/hexane), to obtain the title compound(65 mg) as brown crystals.

[1192]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.25 (s, 3H), 2.33 (s, 3H),2.72 (s, 3H), 3.68 (s, 3H), 4.08 (s, 3H), 6.97 (s, 2H).

Example 360 Ethyl7-[(1-ethylpropyl)amino]-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine-6-carboxylate

[1193] 3-Aminopentane (5 mL) was added to a solution of ethyl7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(1.94 g, 5.22 mmol) in acetonitrile (20 mL), followed by heating underreflux for eight hours. The mixture was extracted with ethyl acetate,and the organic layer was washed with brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (20% ethyl acetate/hexane), to give the titlecompound (1.70 g).

[1194]¹H NMR (400 MHz, CDCl₃) δ0.83 (t, J=7.4 Hz, 6H), 1.43 (t, J=7.1Hz, 3H), 1.35-1.60 (m, 4H), 2.05 (s, 6H), 2.17 (s, 3H), 2.34 (s, 3H),3.02 (s, 3H), 3.92-4.12 (m, 1H), 4.41 (q, J=7.1 Hz, 2H), 6.94 (s, 2H),7.39 (d, J=8.1 Hz, 1H).

Example 3611-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-pyrazolo[1,5-b]purin-2-one

[1195] Hydrazine monohydrate (10 mL) was added to a solution of ethyl7-[(1-ethylpropyl)amino]-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine-6-carboxylate(1.25 g, 2.97 mmol) in ethanol (30 mL), followed by heating under refluxfor five hours. The reaction mixture was evaporated as it was, to give acrude compound. A 10% solution of hydrogen chloride (20 mL) was added toa solution of the crude compound in ethanol (40 mL) under ice-cooling,and a solution of sodium nitrile (229 mg, 3.27 mmol) in water (10 mL)was gradually added dropwise. After one hour, the mixture was stirred atroom temperature for 13 hours. The reaction mixture was evaporated as itwas, and a 2N aqueous solution of sodium hydroxide was added to theresidue. The mixture was extracted with ethyl acetate, and the organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(50% ethyl acetate/hexane) to obtain the title compound (393 mg) asyellow crystals.

[1196] Yellow Crystals

[1197]¹H NMR (400 MHz, CDCl₃) δ0.83 (t, J=7.4 Hz, 6H), 1.68-1.84 (m,2H), 2.02 (s, 6H), 2.08-2.24 (m, 2H), 2.25 (s, 3H), 2.36 (s, 3H), 2.82(s, 3H), 4.20-4.31 (m, 1H), 6.98 (s, 2H), 9.67 (s, 1H).

Example 3621-(1-Ethylpropyl)-6-mesityl-3,4,7-trimethyl-2,3-dihydro-1H-pyrazolo[1,5-b]purin-2-one(CRFA-343)

[1198] Sodium hydride (11.2 mg, 0.28 mmol) was added to a solution ofl-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-pyrazolo[1,5-b]purin-2-one(100 mg, 0.26 mmol) in N,N-dimethylformamide (5 mL) at room temperature.After 30 minutes, methyl iodide (0.018 mL, 0.28 mmol) was added,followed by stirring at the same temperature for one hour. Water wasadded under ice-cooling, and the mixture was extracted with ether. Theorganic layer was washed with brine, dried over anhydrous magnesiumsulfate and evaporated. The residue was purified by silica gel columnchromatography (20-50% ethyl acetate/hexane), to give the title compound(85 mg) and the compound (13 mg) of Example 363 as white crystals.

[1199]¹H NMR (400 MHz, CDCl₃) δ0.78 (t, J=7.4 Hz, 6H), 1.65-1.80 (m,2H), 2.01 (s, 6H), 2.07-2.20 (m, 2H), 2.24 (s, 3H), 2.36 (s, 3H), 3.01(s, 3H), 3.61 (s, 3H), 4.19-4.32 (m, 1H), 6.97 (s, 2H).

Example 3634-Ethyl-1-(1-ethylpropyl)-6-mesityl-3,7-dimethyl-2,3-dihydro-1H-pyrazolo[5,1-b]purin-2-one(CRFA-344)

[1200] Yellow Crystals

[1201]¹H NMR (400 MHz, CDCl₃) δ0.79 (t, J=7.4 Hz, 6H), 1.56 (t, J=7.4Hz, 3H), 1.66-1.80 (m, 2H), 2.02 (s, 6H), 2.04-2.18 (m, 2H), 2.23 (s,3H), 2.36 (s, 3H), 3.46 (q, J=7.4 Hz, 2H), 3.60 (s, 3H), 4.16-4.32 (m,1H), 6.97 (s, 2H).

Example 3643-Benzyl-1-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-pyrazolo[5,1-b]purin-2-one

[1202] Sodium hydride (28 mg, 0.71 mmol) was added to a solution of1-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-pyrazolo[5,1-b]purin-2-one(230 mg, 0.59 mmol) in N,N-dimethylformamide (5 mL) at room temperature.After 30 minutes, benzyl bromide (0.079 mL, 0.65 mmol) was added,followed by stirring at 70° C. for one hour. Water was added underice-cooling, followed by extracting with ethyl acetate. The organiclayer was washed with brine, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel column chromatography(15-20% ethyl acetate/hexane) to give the title compound (259 mg) asbrown crystals.

[1203]¹H NMR (400 MHz, CDCl₃) δ0.83 (t, J=7.3 Hz, 6H), 1.66-1.90 (m,2H), 2.02 (s, 6H), 1.95-2.20 (m, 2H), 2.21 (s, 3H), 2.36 (s, 3H), 2.69(s, 3H), 4.26-4.46 (m, 1H), 5.26 (s, 2H), 6.98 (s, 2H), 7.14-7.46 (m,5H).

Example 3656-Mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]prymidin-3-one

[1204] Hydrazine monohydrate (5 mL) was added to a solution of ethyl7-chloro-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-carboxylate(343 mg, 0.922 mmol) in ethanol (10 mL), followed by stirring at roomtemperature for one hour. The reaction mixture was evaporated as it was,and extracted with ethyl acetate. The organic layer was washed withbrine, dried over anhydrous magnesium sulfate and evaporated. Theresidue was purified by silica gel column chromatography (ethylacetate), to give the title compound (298 mg) as brown crystals.

[1205]¹H NMR (400 MHz, CDCl₃) δ2.03 (s, 6H), 2.22 (s, 3H), 2.50 (s, 3H),3.09 (s, 3H), 7.13 (s, 2H).

Example 366 6-Mesityl-4,7-dimethyl-1H-dipyrazolo[1,5-a:4,3-e]pyrimidine

[1206] One droplet of N,N-dimethylaniline was added to a solution of6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(60 mg, 0.187 mmol) in phosphorus oxychloride (3 mL), followed byheating under reflux for two hours. The reaction mixture was added toice, stirred for a while, and then extracted with ethyl acetate. Theorganic layer was washed with an aqueous saturated solution of sodiumbicarbonate and brine, dried over anhydrous magnesium sulfate andevaporated. Ammonium formate (70 mg, 1.12 mmol) and 10% Pd—C (60 mg)were added to a solution of the resulting crude compound in methanol (3mL), followed by heating under reflux for one hour. The reaction mixturewas filtered using Celite, and the resulting filtrate was evaporated.The residue was purified by silica gel column chromatography (50% ethylacetate/hexane), to give the title compound (5.5 mg) as yellow crystals.

[1207] MS (ESI) m/z 306 MH⁺

Example 3676-Mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine

[1208] Ammonium formate (15 mg, 0.237 mmol) and 10% Pd—C (14 mg) wereadded to a solution of3-chloro-6-mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine(14 mg, 0.14 mmol) in methanol (5 mL), followed by heating under refluxfor one hour. The reaction mixture was filtered using Celite, and theresulting filtrate was evaporated. The residue was purified by silicagel column chromatography (35% ethyl acetate/hexane), to give the titlecompound (9 mg) as a yellow amorphous.

[1209]¹H NMR (400 MHz, CDCl₃) δ2.04 (s, 6H), 2.34 (s, 3H), 2.35 (s, 3H),3.12 (s, 3H), 3.93 (s, 3H), 7.01 (s, 2H), 8.09 (s, 1H).

Example 3681,2-Di(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidine-3-one(CRFA-395)

[1210] 3-Bromopentane (0.152 mL, 1.184 mmol), potassium carbonate (744mg, 5.38 mmol) and a catalytic amount of lithium iodide were added to asolution of6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(346 mg, 1.076 mmol) in N,N-dimethylformamide (10 mL), followed bystirring at 100° C. for three hours. The mixture was extracted withethyl acetate, and the organic layer was washed with brine, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (10-15% ethyl acetate/hexane), to givethe title compound (107 mg) and the compound (49 mg) of Example 369 asbrown crystals.

[1211]¹H NMR (400 MHz, CDCl₃) δ0.70 (t, J=7.3 Hz, 6H), 1.00 (t, J=7.5Hz, 6H), 1.62-1.90 (m, 8H), 2.04 (s, 6H), 2.29 (s, 3H), 2.36 (s, 3H),3.12 (s, 3H), 4.40-4.52 (m, 1H), 4.84-4.95 (m, 1H), 6.99 (s, 2H).

Example 3692-(1-Ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(CRFA-396)

[1212] Brown Crystals

[1213]¹H-NMR (400 MHz, CDCl₃) δ1.01 (t, J=7.5 Hz, 6H), 1.75-1.90 (m,4H), 2.00 (s, 6H), 2.32 (s, 3H), 2.33 (s, 3H), 3.15 (s, 3H), 4.81-4.89(m, 1H), 6.98 (s, 2H), 8.69 (s, 1H).

Example 3704-Ethyl-2-(1-ethylpropyl)-6-mesityl-3-methoxy-7-methyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine(CRFA-502)

[1214] Sodium hydride (31 mg, 0.766 mmol) was added to a solution of2-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(250 mg, 0.639 mmol) in N,N-dimethylformamide (10 mL) at roomtemperature. After 30 minutes, methyl iodide (0.048 mL, 0.766 mmol) wasadded, followed by stirring at the same temperature for three hours.Water was added under ice-cooling, and the mixture was extracted withethyl acetate. The organic layer was washed with brine, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (10-15% ethyl acetate/hexane), to givethe title compound (19 mg) and the compound (30 mg) of Example 371.

[1215]¹H NMR (400 MHz, CDCl₃) δ0.71 (t, J=7.3 Hz, 6H), 1.56 (t, J=7.5Hz, 3H), 1.62-1.94 (m, 4H), 2.05 (s, 6H), 2.29 (s, 3H), 2.36 (s, 3H),3.58 (q, J=7.5 Hz, 2H), 4.09 (s, 3H), 4.41-4.52 (m, 1H), 6.99 (s, 2H).

Example 3712-(1-Ethylpropyl)-4-isopropyl-6-mesityl-1,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(CRFA-503)

[1216]¹H-NMR (400 MHz, CDCl₃) δ0.91 (t, J=7.3 Hz, 6H), 1.70 (d, J=7.1Hz, 6H), 1.68-1.97 (m, 4H), 2.05 (s, 6H), 2.27 (s, 3H), 2.35 (s, 3H),3.34 (s, 3H), 4.05-4.19 (m, 1H), 4.65-4.78 (m, 1H), 6.98 (s, 2H).

Example 3726-Mesityl-4,7-dimethyl-1-propyl-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-ylpropyl ether

[1217] 3-Bromopropane (0.109 mL, 1.20 mmol), potassium carbonate (753mg, 5.45 mmol) and a catalytic amount of lithium iodide were added to asolution of6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(350 mg, 1.09 mmol) in N,N-dimethylformamide (10 mL), followed bystirring at 100° C. for three hours. After extracting with ethylacetate, the organic layer was washed with brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (10% ethyl acetate/hexane), to give the titlecompound (48 mg).

[1218]¹H NMR (400 MHz, CDCl₃) δ1.01 (t, J=7.4 Hz, 3H), 1.08 (t, J=7.4Hz, 3H), 1.80-1.93 (m, 2H), 1.94-2.10 (m, 2H), 2.01 (s, 6H), 2.24 (s,3H), 2.33 (s, 3H), 2.65 (s, 3H), 4.32 (t, J=6.4 Hz, 2H), 4.72 (t, J=6.9Hz, 2H), 6.97 (s, 2H).

Example 3732-(1-Ethylpropyl)-6-mesityl-4,7-dimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine

[1219] Phosphorus oxycloride (1.06 mL, 11.34 mmol), N,N-dimethylaniline(0.018 mL, 0.142 mmol) and methyltriethylammonium chloride (172 mg,1.134 mmol) were added to a solution of2-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-dipyrazolo[1,5-a:4,3-e]pyrimidin-3-one(222 mg, 0.567 mmol) in acetonitrile (10 mL) followed by heating underreflux for six hours. The reaction mixture was added to ice, stirred forawhile, and then extracted with ethyl acetate. The organic layer waswashed with an aqueous saturated solution of sodium bicarbonate andbrine, dried over anhydrous magnesium sulfate and evaporated. Ammoniumformate (215 mg, 3.40 mmol) and 10% Pd—C (200 mg) were added to asolution of the resulting crude compound in methanol (5 mL), followed byheating under reflux for one hour. The reaction mixture was filteredthrough Celite, and the resulting filtrate was evapaorated. The residuewas purified by silica gel column chromatography (20% ethylacetate/hexane), to give the title compound (6.6 mg).

[1220]¹H NMR (400 MHz, CDCl₃) δ0.62 (t, J=7.3 Hz, 6H), 1.66-1.95 (m,4H), 1.97 (s, 6H), 2.27 (s, 3H), 2.30 (s, 3H), 3.06 (s, 3H), 4.53-4.64(m, 1H), 6.94 (s, 2H), 8.07 (s, 1H).

Example 3747-(1-Ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrimidin-6,8-dione

[1221] 3-Aminopentane (0.283 mL, 2.43 mmol) was added to a solution of3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6,7-dicarboxylic acid(780 mg, 2.21 mmol) in acetic acid (10 mL), followed by stirring at 100°C. for two hours. Water was added thereto, followed by extracting withether. The organic layer was washed with brine, dried over anhydrousmagnesium sulfate and evaporated. The residue was purified by silica gelcolumn chromatography (15% ethyl acetate/hexane), to give the titlecompound (480 mg).

[1222]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.4 Hz, 6H), 1.74-1.87 (m,2H), 1.96 (s, 6H), 1.98-2.14 (m, 2H), 2.33 (s, 3H), 2.34 (s, 3H), 3.20(s, 3H), 4.08-4.18 (m, 1H), 6.96 (s, 2H).

Example 3752-Chloro-1-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-1H-pyrazolo[5,1-b]purine

[1223] Two droplets of N,N-dimethylaniline was added to a solution of1-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-2,3-dihydro-1H-pyrazolo[5,1-b]purin-2-one(100 mg, 0.225 mmol), followed by heating under reflux for seven hours.The reaction mixture was added to ice, stirred for a while, and thenextracted with ethyl acetate. The organic layer was washed with anaqueous saturated solution of sodium bicarbonate and brine, dried overanhydrous magnesium sulfate and evaporated. The residue was purified bysilica gel column chromatography (15% ethyl acetate/hexane), to give thetitle compound (76 mg) as brown crystals.

[1224]¹H NMR (400 MHz, CDCl₃) δ0.76 (t, J=7.4 Hz, 6H), 1.75-1.89 (m,2H), 2.02 (s, 6H), 2.20-2.40 (m, 2H), 2.32 (s, 3H), 2.37 (s, 3H), 3.09(s, 3H), 4.27-4.50 (m, 1H), 6.99 (s, 2H).

Example 3761-(1-Ethylpropyl)-6-mesityl-4,7-dimethyl-1H-pyrazolo[1,5-b]purine

[1225] Ammonium formate (70 mg, 1.11 mmol) and 10% Pd—C (76 mg) wereadded to a solution of2-chloro-1-(1-ethylpropyl)-6-mesityl-4,7-dimethyl-1H-pyrazolo[5,1-b]purine(76 mg, 0.185 mmol) in methanol (5 ml), followed by heating under refluxfor one hour. The reaction mixture was filtered through Celite, and theresulting filtrate was evaporated. The residue was purified by silicagel column chromatography (65% ethyl acetate/hexane), to give the titlecompound (67 mg).

[1226]¹H NMR (400 MHz, CDCl₃) δ0.79 (t, J=7.4 Hz, 6H), 1.82-1.93 (m,4H), 2.03 (s, 6H), 2.33 (s, 3H), 2.37 (s, 3H), 3.15 (s, 3H), 4.36-4.45(m, 1H), 7.00 (s, 2H), 7.95 (s, 1H).

Example 3773-Mesityl-2,5-dimethyl-6,7-dihydrofuro[3,2-e]pyrazolo[1,5-a]pyrimidine

[1227] A solution of6-(2-hydroxyethyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol(500 mg, 1.54 mmol) and thionyl chloride (0.26 mL) in benzene (30 mL)was heated under reflux for two hours. After cooling to roomtemperature, the resulting crystals were collected by filtration. Asuspension of the resulting crystals in 2% sodium carbonate was stirredat room temperature for two hours. The crystals were collected byfiltration and purified by silica gel column chromatography (50-70%ethyl acetate/hexane), to give the title compound (310 mg) as pale browncrystals.

[1228]¹H NMR (400 MHz, CDCl₃) δ1.97 (s, 6H), 2.13 (s, 3H), 2.67 (s, 3H),2.39 (s, 3H), 2.98 (t, J=6.4 Hz, 2H), 3.73 (t, J=6.4 Hz, 2H), 6.89 (s,2H).

Example 3783-Mesityl-2,5,7-trimethyl-6,7-dihydrofuro[3,2-e]pyrazolo[1,5-a]pyrimidine

[1229] According to the method of Example 377, the title compound (66mg) was obtained as pale yellowish brown crystals from6-(2-hydroxypropyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol(300 mg, 0.88 mmol).

[1230]¹H-NMR (400 MHz, CDCl₃) δ1.58 (s, 3H), 1.95 (s, 3H), 1.99 (s, 3H),2.17 (s, 3H), 2.30 (s, 3H), 2.37 (s, 3H), 2.75-2.80 (m, 1H), 3.00-3.05(m, 1H), 4.00-4.05 (m, 1H), 6.93 (s, 2H).

Example 3793-Mesityl-2,5-dimethyl-7-propyl-6,7-dihydrofuro[3,2-e]pyrazolo[1,5-a]pyrimidine

[1231] According to the method of Example 377, the title compound (90mg) was obtained as pale grayish brown crystals from6-(2-hydroxypentyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol(1.00 g, 2.72 mmol).

[1232]¹H-NMR (400 MHz, DMSO-d₆) δ0.88 (t, J=5.4 Hz, 3H), 1.32-1.46 (m,1H), 1.50-1.61 (m, 1H), 1.63-1.84 (m, 2H), 1.93 (s, 3H), 1.94 (s, 3H),1.97 (s, 3H), 2.27 (s, 3H), 2.29 (s, 3H), 2.75-2.85 (m, 1H), 2.90-3.00(m, 1H), 4.29-4.38 (m, 1H), 6.96 (s, 2H).

Example 3803-Mesityl-2,5-dimethyl-6,7-dihydropyrazolo[1,5-a]thieno[3,2-e]pyrimidine

[1233] A solution of7-chloro-6-(2-chloroethyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine(500 mg,1.38 mmol), thiourea (105 mg, 1.38 mmol) and sodium carbonate(180 mg, 1.73 mmol) in ethanol (10 mL) was heated under reflux for onehour. After evaporating, water was added and the resulting crystals werecollected by filtration. The crystals were washed with water, to givethe title compound (436 mg) as white crystals.

[1234]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.27 (s, 3H), 2.32 (s, 3H),2.43 (s, 3H), 3.44 (t, J=8.0 Hz, 2H), 3.68 (t, J=8.0 Hz, 2H), 6.96 (s,2H).

Example 3813-Mesityl-2,5-dimethyl-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyrimidine

[1235] A solution of 4-mesityl-3-methyl-1H-5-pyrazoloamine (200 mg, 0.93mmol) and 2-acetylcyclopentanone (0.12 mL, 0.10 mmol) in toluene (2 mL)was heated under reflux for seven hours. The reaction mixture wasevaporated, and the resulting crystals were washed with a mixed solventof ethyl acetate/hexane, to give the title compound (88 mg) as grayishwhite crystals.

[1236]¹H NMR (400 MHz, CDCl₃) δ2.00 (s, 6H), 2.28 (s, 3H), 2.33 (s, 3H),2.34 (tt, J=7.2 Hz, 8.0 Hz, 2H), 3.01 (t, J=7.2 Hz, 2H), 3.42 (t, J=8.0Hz, 2H), 6.97 (s, 2H).

[1237] MS (ESI) m/z 306 MH⁺

Example 3822-(3-Mesityl-2,5-dimethyl-8-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethylmethyl ether

[1238]7-Chloro-6-(3-chlorohexyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidine(170 mg, 0.406 mmol) was dissolved in 2-methoxyethylamine (2 mL),followed by heating under reflux for one hour. Water was added to thereaction mixture, followed by extracting with ethyl acetate. The organiclayer was washed with water and brine, dried over anhydrous magnesiumsulfate and evaporated, to give a pale yellow oil. The oil was dissolvedin N,N-dimethylformamide (10 mL), and sodium iodide (62 mg, 0.416 mmol)and potassium carbonate (172 mg, 1.25 mmol) were added thereto. Themixture was stirred at 150° C. for two days. After cooling, water wasadded to the reaction mixture and extracted with ethyl acetate. Theorganic layer was washed with water and brine, dried over anhydrousmagnesium sulfate, and then evaporated. The residue was purified bysilica gel column chromatography (5-10% ethyl acetate/hexane), to givethe title compound (60 mg, 0.143 mmol) as a pale yellow oil.

[1239]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 3H), 1.30-1.65 (m,4H), 1.90-1.96 (m, 2H), 2.02 (s, 3H), 2.03 (s, 3H), 2.19 (s, 3H), 2.32(s, 3H), 2.36 (s, 3H), 2.50-2.68 (m, 2H), 3.37 (s, 3H), 3.45-3.55 (m,1H), 3.65-3.85 (m, 2H), 3.92-4.01 (m, 1H), 4.35-4.45 (m, 1H), 6.95 (s,2H).

[1240] MS (ESI) m/z 421 MH⁺

[1241] According to the method of Example 382, the title compounds ofExamples 383 to 458 were synthesized.

Example 3833-Mesityl-2,5-dimethyl-9-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1242]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 3H), 1.76-1.86 (m,2H), 1.95-2.03 (m, 2H), 2.01 (s, 6H), 2.20 (s, 3H), 2.32 (s, 3H), 2.34(s, 3H), 2.66 (t, J=6.2 Hz, 2H), 3.38-3.42 (m, 2H), 4.00-4.05 (m, 2H),6.94 (s, 2H).

Example 3849-Butyl-3-mesityl-2,5-dimethyl6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1243]¹H NMR (400 MHz, CDCl₃) δ0.97 (t, J=7.2 Hz, 3H), 1.33-1.42 (m,2H), 1.72-1.80 (m, 2H), 1.95-2.03 (m, 2H), 2.01 (s, 6H), 2.19 (s, 3H),2.32 (s, 3H), 2.34 (s, 3H), 2.66 (t, J=6.2 Hz, 2H), 3.38-3.42 (m, 2H),4.00-4.05 (m, 2H), 6.94 (s, 2H).

Example 3852-(3-Mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethylmethyl ether

[1244]¹H NMR (400 MHz, CDCl₃) δ1.95-2.02 (m, 2H), 2.00 (s, 6H), 2.19 (s,3H), 2.32 (s, 3H), 2.35 (s, 3H), 2.66 (t, J=6.2 Hz, 2H), 3.38 (s, 3H),3.48-3.52 (m, 2H), 3.81 (t, J=6.2 Hz, 2H), 4.21 (t, J=6.2 Hz, 2H), 6.95(s, 2H).

Example 3869-(sec-Butyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1245]¹H-NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 3H), 1.28 (d, J=6.8Hz, 3H), 1.56-1.84 (m, 2H), 1.90-2.06 (m, 2H), 2.02 (s, 6H), 2.19 (s,3H), 2.32 (s, 3H), 2.33 (s, 3H), 2.63-2.69 (m, 2H), 3.26-3.40 (m, 2H),5.86-5.94 (m, 1H), 6.95 (s, 2H).

Example 387 9-Ethyl-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1246]¹H NMR (400 MHz, CDCl₃) δ1.34 (t, J=6.8 Hz, 3H), 1.95-2.02 (m,2H), 2.00 (s, 6H), 2.20 (s, 3H), 2.31 (s, 3H), 2.34 (s, 3H), 2.66 (t,J=6.4 Hz, 2H), 3.36-3.40 (m, 2H), 4.03 (q, J=6.8 Hz, 2H), 6.94 (s, 2H).

Example 3889-Isopropyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1247]¹H-NMR(400 MHz, CDCl₃) δ1.31 (d, J=6.8 Hz, 6H), 1.94-2.02 (m, 2H),2.03 (s, 6H), 2.20 (s, 3H), 2.32 (s, 3H), 2.35 (s, 3H), 2.66 (t, J=6.2Hz, 2H), 3.33-3.37 (m, 2H), 5.89-5.96 (m, 1H), 6.94 (s, 2H).

Example 3893-Mesityl-2,5-dimethyl-8,9-dipropyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1248]¹H NMR (400 MHz, CDCl₃) δ0.93 (t, J=6.8 Hz, 3H), 0.95 (t, J=7.2Hz, 3H), 1.35-1.50 (m, 2H), 1.53-1.72 (m, 3H), 1.82-2.00 (m, 3H), 2.03(s, 6H), 2.20 (s, 3H), 2.31 (s, 3H), 2.36 (s, 3H), 2.52-2.68 (m, 2H),3.34-3.40 (m, 1H), 3.78-3.86 (m, 1H), 3.98-4.04 (m, 1H), 6.94 (s, 2H).

Example 3909-Benzyl-3-mesityl-2,5-dimethyl-8-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1249]¹H NMR (400 MHz, CDCl₃) δ0.78 (t, J=6.8 Hz, 3H), 1.18-1.34 (m,4H), 1.47-1.54 (m, 1H), 1.60-1.72 (m, 2H), 1.77-1.85 (m, 1H), 2.05 (s,3H), 2.07 (s, 3H), 2.23 (s, 3H), 2.33 (s, 3H), 2.39 (s, 3H), 2.54-2.60(m, 2H), 3.34-3.40 (m, 1H), 5.15-5.20 (m, 1H), 5.34-5.44 (m, 1H), 6.94(s, 2H), 7.28-7.38 (m, 3H), 7.43-7.47 (m, 2H).

Example 3919-Ethyl-3-mesityl-2,5-dimethyl-8-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1250]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.2 Hz, 3H), 1.35 (t, J=7.2Hz, 3H), 1.35-1.50 (m, 2H), 1.55-1.70 (m, 2H), 1.80-2.00 (m, 2H), 2.03(s, 6H), 2.22 (s, 3H), 2.33 (s, 3H), 2.38 (s, 3H), 2.52-2.68 (m, 2H),3.32-3.40 (m, 1H), 3.90-4.10 (m, 2H), 6.94 (s, 2H).

Example 3929-Cyclopropylmethyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1251]¹H-NMR (400 MHz, CDCl₃) δ0.25-0.30 (m, 1H), 0.47-0.52 (m, 1H),0.85-0.90 (m, 2H), 1.15-1.30 (m, 2H), 2.01 (s, 6H), 2.01-2.08 (m, 2H),2.20 (s, 3H), 2.31 (s, 3H), 2.36 (s, 3H), 2.67 (t, J=6.0 Hz, 2H),3.48-3.53 (m, 2H), 3.97-4.03 (m, 2H), 6.94 (s, 2H).

Example 3933-Mesityl-2,5,9-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1252]¹H-NMR (400 MHz, CDCl₃) δ1.98-2.05 (m, 2H), 2.02 (s, 6H), 2.22 (s,3H), 2.33 (s, 3H), 2.36 (s, 3H), 2.67 (t, J=6.0 Hz, 2H), 3.35-3.39 (m,2H), 3.62 (s, 3H), 6.96 (s, 2H).

Example 3942-(8-Ethyl-3-mesityl-2,5-methyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethylmethyl ether

[1253]¹H-NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.6 Hz, 3H), 1.37-1.45 (m,1H), 1.60-1.70 (m, 1H), 1.90-2.05 (m, 2H) 2.03 (s, 6H), 2.20 (s, 3H),2.33 (s, 3H), 2.36 (s, 3H), 2.50-2.68 (m, 2H), 3.38 (s, 3H), 3.38-3.50(m, 1H), 3.70-3.85 (m, 2H), 3.90-4.03 (m, 1H), 4.40-4.50 (m, 1H), 6.96(s, 2H).

Example 3958-Ethyl-3mesityl-2,5-dimethyl-9-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1254]¹H-NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.2 Hz, 3H), 1.01 (t, J=7.2Hz, 3H), 1.40-1.50 (m, 1H), 1.60-1.70 (m, 2H), 1.80-2.05 (m, 3H), 2.03(s, 3H), 2.04 (s, 3H), 2.21 (s, 3H), 2.33 (s, 3H), 2.36 (s, 3H),2.50-2.68 (m, 2H), 3.25-3.32 (m, 1H), 3.80-3.88 (m, 1H), 4.00-4.12 (m,1H), 6.96 (s, 2H).

Example 3968,9-Diethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1255]¹H-NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.2 Hz, 3H), 1.34 (t, J=7.2Hz, 3H), 1.38-1.48 (m, 1H), 1.58-1.70 (m, 1H), 1.80-1.90 (m, 1H),1.95-2.02 (m, 1H), 2.02 (s, 3H), 2.03 (s, 3H), 2.21 (s, 3H), 2.32 (s,3H), 2.35 (s, 3H), 2.50-2.68 (m, 2H), 3.25-3.30 (m, 1H), 3.90-4.08 (m,2H), 6.95 (s, 2H).

Example 3979-(Cyclopropylmethyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1256]¹H-NMR (400 MHz, CDCl₃) δ0.12-0.15 (m, 1H), 0.38-0.46 (m, 2H),0.48-0.56 (m, 1H), 1.02 (t, J=7.2 Hz, 3H), 1.14-1.23 (m, 1H), 1.23-1.28(m, 1H), 1.38-1.48 (m, 1H), 1.63-1.73 (m, 1H), 1.96-2.03 (m, 1H), 2.02(s, 6H), 2.20 (s, 3H), 2.32 (s, 3H), 2.37 (s, 3H), 2.52-2.70 (m, 2H),3.41-3.48 (m, 1H), 3.83 (dd, J=6.2, 14.4 Hz, 1H), 4.22 (dd, J=7.7, 14.4Hz, 1H), 6.95 (s, 2H).

Example 3983-Mesityl-9-(2-methoxyethyl)-8-(methoxymethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1257]¹H-NMR (400 MHz, CDCl₃) δ1.88-2.00 (m, 1H), 2.01 (s, 3H), 2.02 (s,3H), 2.12-2.22 (m, 1H), 2.19 (s, 3H), 2.32 (s, 3H), 2.36 (s, 3H),2.50-2.73 (m, 2H), 3.28-3.38 (m, 1H), 3.36 (s, 3H), 3.37 (s, 3H),3.50-3.55 (m, 1H), 3.68-3.76 (m, 1H), 3.77-3.86 (m, 2H), 4.06-4.13 (m,1H), 4.38-4.46 (m, 1H), 6.95 (s, 2H).

Example 3993-Mesityl-2,5,8-trimethyl-9-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1258] MS (ESI) m/z 377 MH⁺

Example 4009-Butyl-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1259] MS (ESI) m/z 391 MH⁺

Example 4012-(3-Mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethylmethyl ether

[1260] MS (ESI) m/z 393 MH⁺

Example 4023-(3-Mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)propylmethyl ether

[1261] MS (ESI) m/z 407 MH⁺

Example 4039-(2-Isopropoxyethyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1262] MS (ESI) m/z 421 MH⁺

Example 4049-Isopentyl-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1263] MS (ESI) m/z 405 MH⁺

Example 4053-Mesityl-2,5,8-trimethyl-9-(1-phenylethyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-]pyrimidine

[1264] MS (ESI) m/z 439 MH⁺

Example 4063-(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)propylmethyl ether

[1265] MS (ESI) m/z 421 MH⁺

Example 4072-(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-y-)ethylisopropyl ether

[1266] MS (ESI) m/z 435 MH⁺

Example 4088-Ethyl-9-isopentyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1267] MS (ESI) m/z 419 MH⁺

Example 4098-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1268] MS (ESI) m/z 453 MH⁺

Example 4109-(1-Benzylpropyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1269] MS (ESI) m/z 481 MH⁺

Example 4113-Mesityl-8-(methoxymethyl)-9-(3-methoxypropyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1270] MS (ESI) m/z 437 MH⁺

Example 4129-(2-Isopropoxyethyl)-3-mesityl-8-(methoxymethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1271] MS (ESI) m/z 451 MH⁺

Example 4139-Isopentyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl)methylmethyl ether

[1272] MS (ESI) m/z 435 MH⁺

Example 4149-Ethyl-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1273] MS (ESI) m/z 363 MH⁺

Example 415(3-Mesityl-2,5-dimethyl-9-propyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl)methylmethyl ether

[1274] MS (ESI) m/z 407 MH⁺

Example 416(9-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl)methylmethyl ether

[1275] MS (ESI) m/z 393 MH⁺

Example 4179-Butyl-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1276] MS (ESI) m/z 405 MH⁺

Example 4188-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1277] MS (ESI) m/z 419 MH⁺

Example 4198-Ethyl-9-(1-ethylpropyl)-1-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1278] MS (ESI) m/z 419 MH⁺

Example 4202-(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethylpropyl ether

[1279] MS (ESI) m/z 435 MH⁺

Example 4219-(Cyclohexylmethyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1280] MS (ESI) m/z 445 MH⁺

Example 4228-Ethyl-1-mesityl-2,5-dimethyl-9-(2-phenylpropyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1281] MS (ESI) m/z 467 MH⁺

Example 4239-(1-Ethylpropyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1282] MS (ESI) W/z 405 MH⁺

Example 4248-Ethyl-9-(2-ethylbutyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1283] MS (ESI) m/z 433 MH⁺

Example 4259-(3,3-Dimethylbutyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1284] MS (ESI) m/z 433 MH⁺

Example 4268-Ethyl-3-mesityl-2,5-dimethyl-9-(tetrahydro-2-franylmethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1285] MS (ESI) m/z 433 MH⁺

Example 4274-[2-(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethyl]morpholine

[1286] MS (ESI) m/z 462 MH⁺

Example 4282-[(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethyl]phenylmethyl ether

[1287] MS (ESI) m/z 469 MH⁺

Example 4293-[(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)ethyl]phenylmethyl ether

[1288] MS (ESI) m/z 469 MH⁺

Example 4304-[(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl)methyl]phenylmethyl ether

[1289] MS (ESI) m/z 469 MH⁺

Example 4318-Ethyl-3-mesityl-2,5-dimethyl-9-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1290] MS (ESI) m/z 431 MH⁺

Example 4329-(2-Ethoxyethyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1291] MS (ESI) m/z 421 MH⁺

Example 4339-(2-Ethylbutyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1292] MS (ESI) m/z 419 MH⁺

Example 4343-Mesityl-2,5,8-trimethyl-9-(tetrahydro-2-furanylmethyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1293] MS (ESI) m/z 419 MH⁺

Example 4359-(2-Ethoxyethyl)-3-mesityl-8-(methoxymethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1294] MS (ESI) m/z 451 MH⁺

Example 436[9-(2-Ethylbutyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl]methylmethyl ether

[1295] MS (ESI) m/z 449 MH⁺

Example 437[3-Mesityl-2,5-dimethyl-9-(tetrahyro-2-furanylmethyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl]methylmethyl ether

[1296] MS (ESI) m/z 449 MH⁺

Example 4389-(Cyclopropylmethyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1297] MS (ESI) m/z 389 MH⁺

Example 4399-(2-Ethoxyethyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1298] MS (ESI) m/z 407 MH⁺

Example 4409-(2-Ethoxyethyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrid[3,2-e]pyrimidine

[1299] MS (ESI) m/z 421 MH⁺

Example 4419-(2-Ethoxyethyl)-3-mesityl-8-(methoxymethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1300] MS (ESI) m/z 437 MH⁺

Example 4429-(3-Ethoxypropyl)-3-mesityl-2,5,8-trimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1301] MS (ESI) m/z 421 MH⁺

Example 4439-(3-Ethoxypropyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1302] MS (ESI) m/z 435 MH⁺

Example 4449-(3-Ethoxypropyl)-3-mesityl-8-(methoxymethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1303] MS (ESI) m/z 451 MH⁺

Example 445[9-(Cyclopropylmethyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8-yl]methylmethyl ether

[1304] MS (ESI) m/z 419 MH⁺

Example 4464-[(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl]methyl]-1-benzenesulfonamide

[1305] MS (ESI) m/z 518 MH⁺

Example 4478-Ethyl-3-mesityl-2,5-dimethyl-9-[4-(trifluoromethyl)benzyl]-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1306] MS (ESI) m/z 507 MH⁺

Example 4489-(4-Chlorobenzyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1307] MS (ESI) m/z 473 MH⁺

Example 4498-Ethyl-3-mesityl-2,5-dimethyl-9-[3-(trifluoromethyl)benzyl]-6,7,8,9-tetrahydropyrazolo-[1,5-a]pyrido[3,2-e]pyrimidine

[1308] MS (ESI) m/z 507 MH⁺

Example 4509-(3-Chlorobenzyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1309] MS (ESI) m/z 473 MH⁺

Example 4518-Ethyl-3-mesityl-2,5-dimethyl-9-(methylbenzyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1310] MS (ESI) m/z 453 MH⁺

Example 4523-[(8-Ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrid[3,2-e]pyrimidin-9-yl)methyl]phenyltrifluoromethyl ether

[1311] MS (ESI) m/z 523 MH⁺

Example 4533-(2-Bromo-4,6-dimethylphenyl)-8-ethyl-9-(2-methoxyethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1312] MS (ESI) m/z 470 M⁺

Example 4543-(2-Bromo-4,6-dimethylphenyl)-9-(cyclopropylmethyl)-8-ethyl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1313] MS (ESI) m/z 466 M+

Example 4558-Ethyl-3-(4-methoxy-2,6-dimethylphenyl)-9-(2-methoxyethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1314] MS (ESI) m/z 423 MH⁺

Example 4568-Ethyl-3-(4-methoxy-2,6-dimethylphenyl)-9-(cyclopropylmethyl)-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1315] MS (ESI) m/z 419 MH⁺

Example 4572-[8-(Cyclopropylmethyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-9-yl]ethylmethyl ether

[1316] MS (ESI) m/z 433 MH⁺

Example 4588,9-Di(cyclopropylmethyl)-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine

[1317] MS (ESI) m/z 429 MH⁺

Example 45910-Butyl-3-mesityl-2,5-dimethyl-7,8,9,10-tetrahydro-6H-pyrazolo[5′,1′-:2,3]pyrimido[4,5-b]azepine

[1318] Sodium iodine (catalytic amount) and potassium carbonate (65 mg,0.47 mmol) were added to a solution ofN-butyl-N-(6-(4-chlorobutyl)-3-mesityl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)amine(65 mg, 0.15 mmol) in 1-methyl-2-piperidone (2 mL), followed by stirringat 150° C. for four hours. Then, the mixture was treated with water,extracted with ethyl acetate, dried over anhydrous magnesium sulfate andevaporated. The residue was purified by silica gel chromatography (15%ethyl acetate/hexane), to give the title compound (18 mg) as yellowcrystals.

[1319]¹H NMR (400 MHz, CDCl₃) δ0.89 (t, J=7.2 Hz, 3H), 1.26-1.36 (m,2H), 1.65-1.74 (m, 2H), 1.76-1.90 (m, 4H), 1.95 (s, 6H), 2.15 (s, 3H),2.25 (s, 3H), 2.34 (s, 3H), 2.75 (t, J=5.6 Hz, 2H), 3.49 (t, J=6.0 Hz,2H), 3.69 (t, J=8.0 Hz, 2H), 6.87 (s, 2H).

Example 4601-(1-Ethylpropyl)-4,8-dimethyl-6-(2,4,6-trichlorophenyl)-1,2,3,6-tetrahydropyrazolo[3,4-b]pyrrolo[2,3-d]pyridine

[1320]4-Chloro-5-(2,chloroethyl)-3,6-dimethyl-1-(2,4,6-trichlorophenyl-1H-pyrazolo[3,4-b]pyridine(185 mg, 0.437 mmol) was dissolved in 3-aminopentane (6 mL), followed byadding p-toluenesulfonic acid (185 mg, 1.074 mmol). The mixture wassealed in a tube at 200° C. for six hours. Water was added to thereaction mixture, followed by extracting with ethyl acetate. The organiclayer was washed with water and brine, dried over anhydrous magnesiumsulfate, and then evaporated. The residue was purified by silica gelcolumn chromatography (10% ethyl acetate/hexane), to give the titlecompound (145 mg, 0.331 mmol) as white crystals.

[1321]¹H NMR (400 MHz, CDCl₃) δ0.96 (t, J=7.6 Hz, 6H), 1.60-1.75 (m,4H), 2.29 (s, 3H), 2.73 (s, 3H), 3.04 (t, J=8.8 Hz, 2H), 3.60 (t, J=8.8Hz, 2H), 4.20-4.30 (m, 1H), 7.47 (s, 2H).

Example 4611-(1-Ethylpropyl)-4,8-dimethyl-6-(2,4,6-trichlorophenyl)-1,6-dihydropyrazolo[3,4-b]pyrrolo[2,3-d]pyridine

[1322]1-(1-Ethylpropyl)-4,8-dimethyl-6-(2,4,6-trichlorophenyl)-1,2,3,6-tetrahydropyrazolo[3,4-b]pyrrolo[2,3,-d]pyridine(70 mg,0.160 mmol) was dissolved in toluene (7 mL). Manganese dioxide(700 mg) was added thereto, followed by stirring at 40° C. overnight.The reaction mixture was filtered through Celite and washed with ethylacetate. The filtrate was evaporated, and the residue was purified bysilica gel column chromatography (5% ethyl acetate/hexane), to give thetitle compound (48 mg, 0.110 mmol) as white crystals.

[1323]¹H NMR (400 MHz, CDCl₃) δ0.88 (t, J=7.2 Hz, 6H), 1.85-2.05 (m,4H), 2.73 (s, 3H), 2.92 (s, 3H), 4.88-4.95 (m, 1H), 6.78 (bs, 1H), 7.10(d, J=5.0 Hz, 1H), 7.52 (s, 2H).

Example 4621-(1-Ethypropyl)-6-mesityl-4,8-dimethyl-2,3-dihydro-1H-imidazo[1,5-a]pyrrolo[3,2-e]pyrimidine

[1324] A solution of4-chloro-3-(2-chloroethyl)-8-mesityl-2,6-dimethylimidazo[1,5-a]pyrimidine(139 mg, 0.38 mmol) in 3-aminopentane (10 mL) was heated under refluxfor five days. After evaporating, the residue was purified by dry packsilica gel column chromatography (25-40% ethyl acetate/hexane), to givethe title compound (69 mg) as pale yellow crystals.

[1325]¹H NMR (400 MHz, CDCl₃) δ0.90 (t, J=7.6 Hz, 6H), 1.50-1.68 (m,4H), 2.10 (s, 6H), 2.29 (s, 3H), 2.30 (s, 3H), 2.95 (s, 3H), 2.95 (t,J=7.2 Hz, 2H), 3.58-3.66 (m, 1H), 3.64 (t, J=7.2 Hz, 2H), 6.90 (s, 2H).

Example 4631-(1-Ethylpropyl)-6-mesityl-4,8-dimethyl-1H-imidazo[1,5-a]pyrrolo[3,2-e]primidine

[1326] Manganese dioxide (67 mg, 0.77 mmol) was added to a solution of1-(1-ethylpropyl)-6-mesityl-4,8-dimethyl-2,3-dihydro-1H-imidazo[1,5-a]pyrrolo[3,2-e]pyrimidine(58 mg, 0.15 mmol) in toluene (10 mL), followed by heating under refluxfor three days. After filtering through Celite, the mixture wasevaporated. The residue was purified by silica gel column chromatography(30% ethyl acetate/hexane), to give the title compound (22 mg) as paleyellow crystals.

[1327]¹H NMR (400 MHz, CDCl₃) δ0.83 (t, J=7.6 Hz, 6H), 1.83-2.06 (m,4H), 2.12 (s, 6H), 2.31 (s, 3H), 2.55 (s, 3H), 3.11 (s, 3H), 4.85-4.94(m, 1H), 6.64 (d, J=3.6 Hz, 1H), 6.84 (d, J=3.6 Hz, 1H), 6.92 (s, 2H).

Example 4641-(1-Ethylpropyl)-6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline

[1328]1-(1-Ethylpropyl)-6-iodo-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline(200 mg, 0.526 mmol), mesitylboric acid (95 mg, 0.579 mmol), bariumhydroxide octahydrate (249 mg, 0.782 mmol) andtetrakistriphenylphosphinepalladium (12 mg, 0.01 mmol) were suspendedinto a mixture of dimethoxyethane (6 mL) and water (1 mL), followed bystirring at 80° C. for two days in nitrogen atmosphere. Water was addedto the reaction mixture, followed by extracting with ethyl acetate. Theorganic layer was washed with water and brine, dried over anhydrousmagnesium sulfate, and then evaporated. The residue was purified bysilica gel column chromatography (ethyl acetate), to give the titlecompound (28 mg, 0.08 mmol) as a pale yellow oil.

[1329]¹H NMR (400 MHz, CD₃OD) δ0.98 (t, J=7.6 Hz, 6H), 1.66-1.76 (m,4H), 1.85 (s, 6H), 2.31 (s, 3H), 2.32 (s, 3H), 3.09 (t, J=9.6 Hz, 3H),3.75 (t, J=9.6 Hz, 3H), 4.40-4.50 (m, 1H), 6.91 (s, 2H), 7.19 (dd,J=1.2, 6.8 Hz, 1H), 7.33 (dd, J=6.8, 8.4 Hz, 1H), 8.16 (dd, J=1.2, 8.4Hz, 1H).

Example 4651-(1-Ethylpropyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1330] 1-(1-Ethylpropyl)-6-iodo-4-methyl-1H-pyrrolo[3,2-c]quinoline (170mg, 0.45 mmol), mesitylboric acid (82 mg, 0.50 mmol), barium hydroxideoctahydrate (213 mg, 0.68 mmol) and tetrakistriphenylphosphinepalladium(26 mg, 0.02 mmol) were suspended into a mixture of 1,2-dimethoxyethane(6 mL) and water (1 mL), followed by stirring at 80° C. overnight innitrogen atmosphere. Water was added to the reaction mixture, followedby extracting with ethyl acetate. The organic layer was washed withwater and brine, dried over anhydrous magnesium sulfate, and thenevaporated. The residue was purified by silica gel column chromatography(5% ethyl acetate/hexane), to give the title compound (11 mg, 0.03 mmol)as a pale yellow oil.

[1331]¹H NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.92 (s, 6H),2.00-2.13 (m, 4H), 2.39 (s, 3H), 2.71 (br s, 3H), 5.05-5.14 (m, 1H),6.75 (d, J=2.8 Hz, 1H), 6.99 (s, 2H), 7.28 (d, J=2.8 Hz, 1H), 7.33 (d,J=7.6 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 8.34 (d, J=7.6 Hz, 1H).

Example 4666-(2,4-dichlorophenyl)-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1332]¹H-NMR(400 MHz, CDCl₃) δ0.85-0.97 (m, 6H), 2.00-2.13 (m, 4H), 2.72(s, 3H), 5.04-5.12 (m, 1H), 6.75 (d, J=3.2 Hz, 1H), 7.28 (d, J=3.2 Hz,1H), 7.33 (dd, J=2.0, 8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.47 (d,J=7.6 Hz, 1H), 7.52 (d, J=2.0 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 8.41 (d,J=7.6 Hz, 1H).

Example 4671-(1-Ethylpropyl)-6-(4-methoxy-2,6-dimethylphenyl-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1333]¹H-NMR (400 MHz, CDCl₃) δ0.94 (t, J=7.6 Hz, 6H), 1.93 (s, 6H),1.98-2.13 (m, 4H), 2.70 (s, 3H), 3.87 (s, 3H), 5.05-5.14 (m, 1H), 6.73(s, 2H), 6.74 (d, J=3.2 Hz, 1H), 7.28 (d, J=3.2 Hz, 1H), 7.32 (d, J=8.0Hz, 1H), 7.51 (t, J=8.0 Hz, 1H), 8.34 (d, J=8.0 Hz, 1H).

Example 4682-[6-(2,4-Dichlorophenyl)-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-yl]butylmethyl ether

[1334]¹H-NMR (400 MHz, CDCl₃) δ0.92-1.00 (m, 3H), 2.02-2.12 (m, 1H),2.15-2.26 (m, 1H), 2.72 (s, 3H), 3.37 (br s, 3H), 3.78-3.83 (m, 1H),3.86-3.93 (m, 1H), 5.20-5.38 (m, 1H), 6.75 (d, J=3.2 Hz, 1H), 7.33 (dd,J=2.0, 8.0 Hz, 1H), 7.36 (d, J=3.2 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.47(d, J=7.6 Hz, 1H), 7.52 (d, J=2.0 Hz, 1H), 7.54 (t, J=7.6 Hz, 1H), 8.37(d, J=7.6 Hz, 1H).

Example 4696-(4-Methoxy-2,6-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1335]¹H-NMR (400 MHz, CDCl₃) δ0.99 (t, J=7.6 Hz, 3H), 1.92 (s, 3H),1.94 (s, 3H), 2.05-2.15 (m,1H), 2.17-2.26 (m, 1H), 2.69 (s, 3H), 3.39(s, 3H), 3.81 (dd, J=5, 10.5 Hz, 1H), 3.87 (s, 3H), 3.93 (dd, J=4.5,10.5 Hz, 1H), 5.22-5.30 (m, 1H), 6.73 (s, 2H), 6.74 (d, J=3.2 Hz, 1H),7.33 (d, J=8.0 Hz, 1H), 7.36 (d, J=3.2 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H),8.30 (d, J=8.0 Hz, 1H).

Example 470 2-(6-Mesityl-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-yl)butylmethyl ether

[1336]¹H-NMR (400 MHz, CDCl₃) δ0.99 (t, J=7.2 Hz, 3H), 1.90 (s, 3H),1.92 (s, 3H), 2.05-2.15 (m, 1H), 2.17-2.26 (m, 1H), 2.39 (s, 3H), 2.69(s, 3H), 3.39 (s, 3H), 3.81 (dd, J=4.5, 10.5 Hz, 1H), 3.93 (dd, J=4.5,10.5 Hz, 1H), 5.22-5.30 (m, 1H), 6.74 (d, J=3.2 Hz, 1H), 6.99 (s, 2H),7.33 (d, J=8.0 Hz, 1H), 7.36 (d, J=3.2 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H),8.30 (d, J=8.0 Hz, 1H).

Example 4716-Mesityl-1-[2-methoxy-1-(methoxymethyl)ethyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1337]¹H NMR (400 MHz, CDCl₃) δ1.90 (s, 6H), 2.39 (s, 3H), 2.70 (br s,3H), 3.43 (s, 6H), 3.92-4.02 (m, 4H), 5.45-5.50 (m, 1H), 6.72 (d, J=3.2Hz, 1H), 7.00 (s, 2H), 7.34 (d, J=8.0 Hz, 1H), 7.46 (d, J=3.2 Hz, 1H),7.54 (t, J=8.0 Hz, 1H), 8.29 (d, J=8.0 Hz, 1H).

Example 4721-[2-Ethoxyethyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1338]¹H NMR (400 MHz, CDCl₃) δ1.19 (t, J=7.2 Hz, 3H), 1.91 (s, 6H),2.39 (s, 3H), 2.71 (s, 3H), 3.51 (q, J=7.2 Hz, 2H), 3.98 (t, J=6.0 Hz,2H), 4.77 (t, J=6.0 Hz, 2H), 6.68 (d, J=3.2 Hz, 1H), 7.00 (s, 2H), 7.18(d, J=3.2 Hz, 1H), 7.35 (dd, J=1.2, 7.2 Hz, 1H), 7.54 (dd, J=7.2, 8.4Hz, 1H), 8.22 (dd, J=1.2, 8.4 Hz, 1H).

Example 4736-(4-Methoxy-2,6-dimethylphenyl)-1-[2-methoxy-1-(methoxymethyl)ethyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1339]¹H NMR (400 MHz, CDCl₃) δ1.92 (s, 6H), 2.70 (s, 3H), 3.43 (s, 6H),3.87 (s, 3H), 3.94-4.04 (m, 4H), 5.44-5.50 (m, 1H), 6.72 (d, J=3.2 Hz,1H), 6.73 (s, 2H), 7.34 (dd, J=1.2, 7.2 Hz, 1H), 7.46 (d, J=3.2 Hz, 1H),7.53 (dd, J=7.2, 8.4 Hz, 1H), 8.28 (dd, J=1.2, 8.4 Hz, 1H).

Example 4741-(2-Ethoxyethyl)-6-mesityl-4-methyl-2-propyl-1H-pyrrolo[3,2-c]quinoline

[1340]¹H NMR (400 MHz, CDCl₃) δ1.11 (t, J=7.2 Hz, 3H), 1.20 (t, J=7.2Hz, 3H), 1.78-1.90 (m, 2H), 1.90 (s, 6H), 2.39 (s, 3H), 2.68 (s, 3H),2.85 (t, J=7.6 Hz, 2H), 3.51 (q, J=7.2 Hz, 2H), 3.93 (t, J=6.8 Hz, 2H),4.73 (t, J=6.8 Hz, 2H), 6.47 (s, 1H), 7.00 (s, 2H), 7.31 (dd, J=1.2, 7.2Hz, 1H), 7.53 (dd, J=7.2, 8.4 Hz, 1H), 8.22 (dd, J=1.2, 8.4 Hz, 1H).

Example 4753-(6-Mesityl-4-methyl-2-propyl-1H-pyrrolo[3,2-c]quinolin-1-yl)propylmethyl ether

[1341]¹H NMR (400 MHz, CDCl₃) δ1.11 (t, J=7.6 Hz, 3H), 1.78-1.90 (m,2H), 1.90 (s, 6H), 2.18-2.32 (m, 2H), 2.39 (s, 3H), 2.68-2.76 (m, 2H),2.82 (t, J=7.6 Hz, 2H), 3.42 (s, 3H), 3.45 (t, J=5.6 Hz, 2H), 4.66 (t,J=7.6 Hz, 2H), 6.50 (s, 1H), 7.00 (s, 2H), 7.32 (d, J=8.0 Hz, 1H), 7.56(t, J=8.0 Hz, 1H), 8.34 (d, J=8.0 Hz, 1H).

Example 4761-(2-Isopropoxyethyl)-6-mesityl-4-methyl-2-propyl-1H-pyrrolo[3,2-c]quinoline

[1342]¹H NMR (400 MHz, CDCl₃) δ1.11 (t, J=7.6 Hz, 3H), 1.14 (d, J=4.8Hz, 6H), 1.80-1.90 (m, 2H), 1.91 (s, 6H), 2.39 (s, 3H), 2.68 (s, 3H),2.85 (t, J=7.6 Hz, 2H), 3.52-3.60 (m, 1H), 3.91 (t, J=6.8 Hz, 2H), 4.70(t, J=6.8 Hz, 2H), 6.46 (s, 1H), 7.00 (s, 2H), 7.31 (dd, J=1.6, 7.2 Hz,1H), 7.53 (dd, J=7.2, 8.4 Hz, 1H), 8.22 (dd, J=1.6, 8.4 Hz, 1H).

Example 477N-(5-1-[1-(Methoxymethyl)propyl]-4-methyl-1H-pyrrolo[3,2-c]quinolin-6-yl-4-methyl-2-pyridyl)-N,N-dimethylamine

[1343]¹H NMR (400 MHz, CDCl₃) δ0.92-1.02 (m, 3H), 2.00-2.13 (m, 3H),2.14-2.25 (m, 1H), 2.74 (s, 3H), 3.16 (s, 3H), 3.33-3.40 (m, 3H),3.76-3.85 (m, 1H), 3.87-3.95 (m, 1H), 5.20-5.30 (m, 1H), 6.51 (s, 1H),6.74 (d, J=3.2 Hz, 1H), 7.35 (d, J=3.2 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H),7.52 (t, J=8.0 Hz, 1H), 8.13 (s, 1H), 8.32 (d, J=8.0 Hz, 1H).

Example 478N-5-[1-(1-ethylpropyl)-4-metyl-1H-pyrrolo[3,2-c]quinolin-6-yl]-4-methyl-2-pyrizyl-N,N-dimethylamine

[1344] MS (ESI) m/z 386 M+

Example 4796-(2,4-Dimethoxyphenyl)-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1345] MS (ESI) m/z 388 M⁺

Example 4806-(2,6-Dimethoxy-4-methylphenyl)-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1346] MS (ESI) m/z 402 M⁺

Example 4816-(2,4-Dimethoxy-6-methylphenyl)-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1347] MS (ESI) m/z 402 M⁺

Example 4821-(1-Ethylpropyl)-4-methyl-6-(2,4,6-trimethoxyphenyl)-1H-pyrrolo[3,2-c]quinoline

[1348] MS (ESI) m/z 418 M⁺

Example 4836-[2-Chloro-4-(trifuluoromethyl)phenyl]-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1349] MS (ESI) m/z 430 M⁺

Example 4846-(2-Methoxy-4,6-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1350] MS (ESI) m/z 402 M⁺

Example 4856-(2,4-Dimethoxyphenyl)-1-[1-(methoxymethyl)propyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1351] MS (ESI) m/z 404 M⁺

Example 4862-6-[2-Chloro-4-(trifluoromethyl)phenyl]-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-ylbutylmethyl ether

[1352] MS (ESI) m/z 446 M⁺

Example 4871-(1-Ethylpropyl)-6-(2-methoxy-4,6-dimethylphenyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1353] MS (ESI) m/z 387 MH⁺

Example 4886-Mesityl-4-metyl-1-(1-propylbutyl)-1H-pyrrolo[3,2-c]quinoline

[1354] MS (ESI) m/z 399 MH⁺

Example 4896-(2,6-Dimethoxy-4-methylphenyl)-1-[1-(methoxymethyl)propyl]-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1355] MS (ESI) m/z 418 M⁺

Example 4906-(2,6-Dimethoxy-6-methylphenyl)-1-[1-(methoxymethyl)propyl]-4-methyl-1Hpyrrolo[3,2-c]quinoline

[1356] MS (ESI) m/z 418 M⁺

Example 4911-[1-(Methoxymethyl)propyl]-4-metyl-6-(2,4,6-trimethoxyphenyl)-1H-pyrrolo[3,2-c]quinoline

[1357] MS (ESI) m/z 434 M⁺

Example 4921-(1-Ethylbutyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1358] MS (ESI) m/z 384 M⁺

Example 4936-(2-Bromo-4-isopropylphenyl)-1-(1-ethylpropyl)-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1359] MS (ESI) m/z 448 M⁺

Example 4941-(1-Ethylpropyl)-6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,7]naphthyridine

[1360] A solution of4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,7]naphthyridine (100 mg,0.28 mmol) in 3-aminopentane (5.0 mL) was stirred at 200° C. for sixhours in a sealed tube. After evaporating, the residue was purified bysilica gel column chromatography (30-50% ethyl acetate/hexane), to givethe title compound (104 mg) as pale brown crystals.

[1361]¹H-NMR (400 MHz, CDCl₃) δ1.00 (t, J=7.2 Hz, 6H), 1.60-1.80 (m,4H), 1.91 (s, 6H), 2.35 (s, 3H), 2.38 (s, 3H), 3.09 (t, J=5.6 Hz, 2H),3.72 (t, J=5.6 Hz, 2H), 4.24-4.32 (m, 1H), 6.94 (s, 2H), 7.80 (d, J=6.0Hz, 1H), 8.39 (d, J=6.0 Hz, 1H).

Example 4951-(1-Ethylpropyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridine

[1362] An activated manganese dioxide (108 mg, 1.25 mmol) was added to asolution of1-(1-ethylpropyl)-6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,7]naphthyridine(93 mg, 0.25 mmol) in toluene (9.0 mL) and methylene chloride (3.0 mL)and the mixture was heated under reflux for three days. After filteringthrough Celite, the mixture was evaporated. The residue was purified bysilica gel column chromatography (10% ethyl acetate/hexane), to give thetitle compound (55 mg) as pale brown crystals.

[1363]¹H-NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.6 Hz, 6H), 1.92 (s, 6H),1.98-2.15 (m, 4H), 2.37 (s, 3H), 2.74 (s, 3H), 5.01-5.10 (m, 1H), 6.81(d, J=3.2 Hz, 1H), 6.96 (s, 2H), 7.40 (d, J=3.2 Hz, 1H), 8.10 (d, J=6.0Hz, I1H), 8.64 (d, J6.0 Hz, 1H).

Example 4962-(6-Mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,7]naphthyridin-yl)butylmethyl ether

[1364] According to the method of Example 494, the title compound (34mg) was obtained as white crystals from4-chloro-3-(2-chloroethy)-8-mesityl-2-methyl[1,7]naphthyridine (100 mg,0.28 mmol).

[1365]¹H-NMR(400 MHz, CDCl₃) δ1.04 (t, J=7.6Hz, 3H), 1.65-1.85 (m, 2H),1.90 (s, 3H), 1.92 (s, 3H), 2.35 (s, 3H), 2.41 (s, 3H), 3.12 (t, J=9.6Hz, 2H), 3.36 (s, 3H), 3.57 (dd, J=10.0 Hz, 4.8 Hz, 1H), 3.66 (dd,J=10.0 Hz, 7.2 Hz, 1H), 3.83 (t, J=9.6 Hz, 2H), 4.51-4.60 (m, 1H), 6.94(s, 2H), 7.83 (d, J=6.0 Hz, 1H), 8.42(d, J=6.0 Hz, 1H).

Example 4972-(6-Mesityl-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridin-yl)butyl methylether

[1366] According to the method of Example 495, the title compound (24mg) was obtained as pale yellow crystals from2-(6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,7]naphthyridin-1-yl)butylmethyl ether (30 mg, 0.08 mmol)

[1367]¹H-NMR (400 MHz, CDCl₃) δ0.99 (t, J=7.6 Hz, 3H), 1.91 (s, 3H),1.92 (s, 3H), 2.03-2.28 (m, 2H), 2.37 (s, 3H), 2.73 (s, 3H), 3.38 (s,3H), 3.83 (dd, J=10.0 Hz, 4.8 Hz, 1H), 3.91 (dd, J=10.0 Hz, 6.0 Hz, 1H),5.18-5.27 (m, 1H), 6.81 (d, J=3.2 Hz, 1H), 6.96 (s, 2H), 7.50 (d, J=3.2Hz, 1H), 8.10 (d, J=6.0 Hz, 1H), 8.65(d, J=6.0 Hz, 1H).

Example 4986-Mesityl-1-[2-methoxy-1-(methoxymethyl)ethyl]-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridine

[1368] According to the methods of Examples 495 and 495, the titlecompound (59 mg) was obtained as pale yellow crystals from4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,7]naphthyridine (180 mg,0.50 mmol).

[1369]¹H-NMR(400 MHz, CDCl₃) δ1.91 (s, 6H), 2.37 (s, 3H), 2.73 (s, 3H),3.43 (s, 6H), 3.92-4.02 (m, 4H), 5.39-5.45 ((m, 1H), 6.80 (d, J=3.2 Hz,1H), 6.96 (s, 2H), 7.62 (d, J=3.2 Hz, 1H), 8.11 (d, J=6.0 Hz, 1H), 8.66(d, J=6.0 Hz, 1H).

Example 4991-(1-ethylpropyl)-6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,7]naphthyridine

[1370] Activated manganese dioxide (47 mg, 0.54 mmol) was added to asolution of1-(1-ethylpropyl)-6-mesityl-4-methyl-2,3-dihydro-1H-pyrrolo[3,2-c][1,5]naphthyridine(40 mg, 0.11 mmol) in toluene (4.0 mL) and the mixture was heated underreflux for one day. After filtering through Celite, the mixture wasevaporated. The residue was purified by silica gel column chromatography(10% ethyl acetate/hexane), to give the title compound (32 mg) as whitecrystals.

[1371]¹H-NMR (400 MHz, CDCl₃) δ0.86 (t, J=7.2 Hz, 6H), 1.86-2.10 (m,4H), 1.93 (s, 6H), 2.39 (s, 3H), 2.74 (s, 3H), 6.71-6.62 (m, 1H), 6.76(d, J=3.2 Hz, 1H), 7.00 (s, 2H), 7.25 (d, J=4.8 Hz, 1H), 7.36 (d, J=3.2Hz, 1H), 8.77 (d, J=4.8 Hz, 1H).

Example 5002-(6-Mesityl-4-mesityl-1H-pyrrolo[3,2-c][1,5]naphthyridin-1-yl)butylmethyl ether

[1372] A solution of4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine (200 mg,0.557 mmol) in 2-amino-1-methoxybutane (2.0 mL) was stirred at 200° C.for four hours in a sealed tube. After evaporating, the residue waspurified by silica gel column chromatography (30-50% ethylacetate/hexane). Activated manganese dioxide (290 mg, 3.24 mmol) wasadded to a solution of the resulting product (130 mg, 0.33 mmol) intoluene (20 mL) and the mixture was heated under reflux for one day.After filtering through Celite, the mixture was evaporated. The residuewas purified by silica gel column chromatography (10% ethylacetate/hexane), to give the title compound (108 mg) as white crystals.

[1373]¹H-NMR (400 MHz, CDCl₃) δ0.93 (t, J=7.2 Hz, 3H), 1.91 (s, 3H),1.94 (s, 3H), 1.96-2.18 (m, 2H), 2.39 (s, 3H), 2.74 (s, 3H), 3.37 (s,3H), 3.76-3.94 (m, 2H), 6.75 (d, J=2.4 Hz, 1H), 6.75-6.86 (m, 1H),7.00(s, 2H), 7.25 (d, J=4.8 Hz, 1H), 7.48 (d, J=2.4 Hz, 1H), 8.77 (d,J=4.8 Hz, 1H).

Example 5016-Mesityl-1-[2-methoxy-1-(methoxymethyl)ethyl]-4-methyl-1H-pyrrolo[3,2-c][1,5]naphthyridine

[1374] According to the method of Example 500, the title compound (115mg) was obtained as pale yellow crystals from4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine (200 mg,0.56 mmol).

[1375]¹H-NMR (400 MHz, CDCl₃) δ1.92 (s, 6H), 2.39 (s, 3H), 2.74 (s, 3H),3.41 (s, 6H), 3.90-4.06 (m, 4H), 6.73 (d, J=3.6 Hz, 1H), 7.00 (s, 2H),7.02-7.12 (m, 1H), 7.26 (d, J=4.4 Hz, 1H), 7.57 (d, J=3.6 Hz, 1H), 8.77(d, J=4.4 Hz, 1H).

Example 5026-Mesityl-4-methyl-1-(1-methylpropyl)-1H-pyrrolo[3,2-c][1,7]naphthyridinehydrochloride

[1376] According to the method of Example 500, the title compound (107mg) was obtained as pale yellow crystals from4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine (200 mg,0.56 mmol).

[1377]¹H-NMR(400 MHz, CDCl₃) δ0.92 (t, J=7.2 Hz, 3H), 1.22-1.44 (m, 2H),1.60 (d, J=6.8 Hz, 3H), 1.96-2.18 (m, 2H), 1.91 (s, 3H), 1.95 (s, 3H),2.39 (s, 3H), 2.73 (s, 3H), 6.64-6.76 (m, 1H), 6.74 (d, J=3.2 Hz, 1H),7.00 (s, 2H), 7.26 (d, J=4.4 Hz, 1H), 7.41 (d, J=3.2 Hz, 1H), 8.79 (d,J=4.4 Hz, 1H).

Example 5032-(6-Mesityl-4-methyl-1H-pyrrolo[3,2-c][1,5]naphthyridin-1-yl)propylmethyl ether hydrochloride

[1378] According to the method of Example 500, the, title compound (83mg) was obtained as pale yellow crystals from4-chloro-3-(2-chloroethyl)-8-mesityl-2-methyl[1,5]naphthyridine (200 mg,0.56 mmol).

[1379]¹H-NMR (400 MHz, CDCl₃) δ1.68 (d, J=7.2 Hz, 3H), 1.91 (s, 3H),1.93 (s, 3H), 2.39 (s, 3H), 2.74 (s, 3H), 3.39 (s, 3H), 3.78 (dd, J=10Hz, 4.8 Hz, 1H), 3.89 (dd, J=10 Hz, 5.6 Hz, 1H), 6.74 (d, J=3.2 Hz, 1H),6.78-6.90 (m, 1H), 7.00 (s, 2H), 7.26 (d, J=4.4 Hz, 1H), 7.50 (d, J=3.2Hz, 1H), 8.78 (d, J=4.4 Hz, 1H).

Example 5041-(1-Ethylpropyl)-7-mesityl-4,6-dimethyl-1H-pyrrolo[3,2-c]quinoline

[1380] A solution of4-chloro-3-(2-chloroethyl)-7-mesityl-2,8-dimethylquinoline (200 mg, 0.54mmol) in 3-aminopentane (6.0 mL) was stirred in a sealed tube at 200° C.for 8 hr. After evaporating, activated manganese dioxide (101 mg, 1.16mmol) was added to a solution of the residue in toluene (9.0 mL) and themixture was stirred for two days. After filtering through Celite, themixture was evaporated. The residue was purified by silica gel columnchromatography (10% ethyl acetate/hexane) to give the title compound (12mg) as white crystals.

[1381]¹H-NMR (400 MHz, CDCl₃) δ0.91 (t, J=7.6 Hz, 6H), 1.95 (s, 6H),1.96-2.12 (m, 4H), 2.37 (s, 3H), 2.55 (s, 3H), 2.90 (s, 3H), 5.06-5.14(m, 1H), 6.79 (d, J=3.2 Hz, 1H), 6.99 (s, 2H), 7.17 (d, J=8.0 Hz, 1H),7.28 (d, J=3.2 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H).

Example 5051-(1-Ethylpropyl)-7-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinoline

[1382] A solution of1-(1-ethylpropyl)-7-iodo-4-mesityl-1H-pyrrolo[3,2-c]quinoline (32 mg,0.09 mmol), mesitylboric acid (17 mg, 0.10 mmol), Pd(PPh₃)₄ (5 mg,4.23×10⁻³ mmol) and barium hydroxide octahydrate (40 mg, 0.13 mmol) in2,2-dimethoxyethane (6.0 mL) and water (1.0 mL) was stirred at 80° C.for one day. After filtering through Celite, the filtrate was dilutedwith ethyl acetate, washed with brine, dried over anhydrous magnesiumsulfate and evaporated. The residue was purified by silica gel columnchromatography (10% ethyl acetate/hexane), to give the title compound(17 mg) as white crystals.

[1383]¹H-NMR (400 MHz, CDCl₃) δ0.92 (t, J=7.2 Hz, 6H), 1.96-2.14 (m,4H), 2.06 (s, 6H), 2.36 (s, 3H), 2.90 (s, 3H), 5.05-5.14 (m, 1H), 6.81(d, J=3.2 Hz, 1H), 6.97 (s, 2H), 7.28 (d, J=8.0 Hz, 1H), 7.29 (d, J=3.2Hz, 1H), 7.97 (s, 1H), 8.36 (d, J=8.0 Hz, 1H).

[1384] Test Examples

[1385] The present compounds were evaluated for the ability to bind to acorticotrophin releasing hormone receptor (CRFR) and the adenylatecyclase activity inhibitory ability. Each test procedures and theresults are as follows:

[1386] Test Example 1: CRFR Binding Experiment

[1387] (1) Preparation of CRFR expressing cell: As an experimentmaterial for the CRFR binding experiment, a membrane fraction of a cellwhich expressed highly human CRFR 1. CRFR expressing cell was preparedas follows. The full length gene of CRFR¹ was obtained by a PCT methodusing human brain (QuickClone™ Clontech) as cDNA library. The resultingDNA fragment was inserted into a cloning vector to confirm the basesequence. A cDNA having the correct base sequence was ligated to anexpression vector (pcDNA3.1™, Invitrogen). A gene was inserted into Hek283 cell and grown in a cell culturing solution containing G418 (1mg/ml) to obtain a resistance cell, into which a CRFR¹ expression vectorwas cloned by a limitation diluting method. A clone having the highbinding ability of membrane and sauvagine per unit protein was finallyselected from cloned cells by a binding experiment shown by the methodshown below, which was used for an experiment.

[1388] (2) Preparation of a membrane fraction: G418 resistant cells intowhich a gene for CRFR 1 was introduced were collected, and cell rupturewas performed by an ultrasound generator with a sonicate buffer(D-PBS-10 mM MgCl₂, 2 mM EGTA). A suspension after ultrasound rupturewas centrifuged (46,000×g, 10 minutes), the sediment thereof was furtherresuspended with a sonicate buffer, and the same procedures wererelated. Finally, the sediment was suspended in a binding buffer(D-PBS-10 mM MgCl₂, 2 mM EGTA, 1.5% BSA, 0.15 mM bacitracin, 1×proteaseinhibitor cocktail (COMPLETE™, Boehringer), to adjust the proteinconcentration at 1.6 mg/ml, which was used as a membrane fraction.

[1389] (3) Binding experiment: Binding experiment with sauvagine wasperformed using a 96-well plate and SPA™ (Amersham pharmacia). Anexperiment was according to the specification of SPA beads. 40 mg of amembrane fraction protein, 0.5 mg of beads and 40 pM ¹²⁵I-sauvaging(Amersham pharmacia) were allowed to stand at room temperature for twohours in the presence a test compound, centrifuged (1,000×g, 5 minutes),and then the radioactivity of each well was measured with TopCount™(Packard).

[1390] (4) Calculation of the binding ability: The radioactivity as thenon-specific binding when 1,000-fold excessive amount of non-radioactivesauvagine was added was substacted from each value, the radioactivitywhere no test material is added is regarded as 100% (control), and eachvalue is shown by % (% of control). The concentration showing 50% in %(% of control) was obtained from a graph where the concentration testmaterial is plotted on an abscissa axis and % (% of control) is plottedon a coordinate axis and IC₅₀ value was calculated (Table 1).

[1391] Test Example 2: Experiment for Measuring Adenyrate Cyclase theActivity Using AtT-20cell

[1392] (1) Test procedures: AtT-20 cell is a cell strain derived frommouse pytuitari gland tumor, it is known that the intracellularadenyrate cyclase system is activated in response to corticotrophinrelease hormone (CRF), to produce cyclic AMP (cAMP), releasingadrenocortical hormone(ACTH) (Biochem. Piophys. Res. Com. 106.1364-1371, 1982). In this experiment, the cell (1×10⁵) suspended inD-MEM medium (0.1% FPS), seeded on a 96-well plate, a phosphodiesteraseinhibitor (IBMX, Calbiochem) was added to the final concentration of 1mM, which was cultured at 37° C. for 30 minutes. A diluted test compoundsolution and CRF (30 nM) were added, which was further cultured at 37°C. for 10 minutes, cells were collected by centrifugation (500×g, 5minutes), cells were lysed with a lysis buffer (Amersham Pharmacia), andan amount of intracellular cAMP produced was quantitated using the ELISAmethod. For ELISA, cAMP EIA system (BIOTRAK™ Amersham Pharmacia) wasused.

[1393] (2) Calculation of adenyrate cyclase activity inhibitory ability:Treatment of the resulting data was carried out as follows. An amount ofcAMP produced by a cell to which 30 nM CRF was added is regarded as 100%(control) and a value of each sample is expressed as % (% of control).The concentration showing 50% in % (% of control) was obtained from agraph where the concentration of a test material is plotted on anabscissa axis and % (% of control) is plotted on a coordinate and IC₅₀value was calculated (Table 2). TABLE 1 CRF1 receptor binding abilityEx. No. IC₅₀ (nM) 1 100 2 500 3 600 6 1000 12 1500 13 2500 23 1500 331000 38 3000 44 400 45 1500 67 200 74 1400

[1394] TABLE 2 adenylate cyclase ability Ex. No. IC₅₀ (nM) 1 900 13 150067 2000

[1395] The present compound has an excellent binding ability to CRFR andsignificantly inhibited the adenylate cyclase activity by CRF.

[1396] According to the present invention, novel compounds having theCRF receptor antagonism, a pharmacologically acceptable salt thereof andhydrates thereof can be provided. The compound of the present invention,a pharmacologically acceptable salt thereof or hydrates thereof have anexcellent antagonism to a CRF receptor, are low toxic, highly safe andhighly useful as a drug. Therefore, the compounds of the presentinvention are useful as an agent for treating or preventing diseases towhich CRF and/or its receptor relate. In particular, they are useful asan agent for treating or preventing depression, depressive symptom(great depression, monostotic depression, recurrent depression, infanttyrannism by depression, postpartum depression etc.), mania, anxiety,generalized anxiety disorder, panic disorder, phobia, compulsivedisorder, posttraumatic stress disorder, Tourette syndrome, autism,emotional disorder, sentimental disorder,,bipolar disorder, cyclothymia,schizophrenia, peptic ulcer, irritable bowel syndrome, ulcerativecolitis, Crohn's disease, diarrhea, coprostasis, postoperational ileus,gastrointestinal function abnormality associated with stress, neuralvomiting etc.

1. A compound represented by the formula:

(wherein A, B and D are the same as or different from each other andeach represents: (1) heteroatom selected from nitrogen atom, oxygen atomand sulfur atom; (2) formula —(CR¹R²)_(m)— (wherein R¹ and R² are: (i)the same as or different from each other and each represents hydrogenatom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynyl group, aC₁₋₆ alkoxy group, a C₃₋₈ cycloalkyl group, a C₁₋₆ alkoxy C₁₋₆ alkylgroup, a C₃₋₈ cycloalkyl C₁₋₆ alkyl group or a C₁₋₆ alkyl-aryl group, orR¹ and R² may be bound together to form a 3- to 8-membered ring; (ii)R¹s are bound together so that adjacent —CR¹R²-s form a carbon-carbondouble bond, that is, a partial structure represented by formula—CR²═CR²—; or (iii) R¹ and nitrogen atom may form a bond so that anadjacent nitrogen atom and —CR¹R²— form a partial structure representedby the formula —N═CR²— (R² is as defined above); and m is 0 or aninteger of 1 to 4); (3) —CO—; (4) —CS—; (5) —NR³— (wherein R³represents: (i) hydrogen atom; (ii) formula —COR⁴ (wherein R⁴ representsa C₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄ alkyl group, anoptionally substituted aryl group, an optionally substituted heteroarylC₁₋₄ alkyl group or an optionally substituted heteroaryl group); (iii)—S(O)_(n)R⁵ (wherein R⁵ represents a C₁₋₆ alkyl group, an optionallysubstituted aryl C₁₋₄ alkyl group, an optionally substituted aryl group,an optionally substituted heteroaryl C₁₋₄ alkyl group or an optionallysubstituted heteroaryl group; and n is an integer of 0, 1 or 2); (iv) aC₁₋₁₀ alkyl group optionally substituted with any of one or more groupsdefined in the following A group; (v) a C₂₋₁₀ alkenyl group optionallysubstituted with any of one or more groups defined in the following Agroup; (vi) a C₂₋₁₀ alkynyl group optionally substituted with any of oneor more groups defined in the following A group; (vii) an optionallysubstituted aryl group; or (viii) a C₃₋₈ cycloalkyl group optionallyfused with optionally substituted benzene ring and optionallysubstituted with a C₁₋₄ alkyl group); (6) —SO—; or (7) —SO₂—, E and Gare the same as or different from each other and each represents: (1) aheteroatom selected from nitrogen atom, oxygen atom and sulfur atom; (2)formula —(CR⁶R⁷)_(p)— (wherein R⁶ and R⁷ are: (i) the same as ordifferent from each other and each represents hydrogen atom, a C₁₋₆alkyl group, a C₃₋₈ cycloalkyl group optionally substituted with a C₁₋₄alkyl group, an optionally substituted aryl group or an optionallysubstituted heteroaryl group; (ii) R⁶s are bound together so thatadjacent —CR⁶R⁷-s form a carbon-carbon double bond, that is, a partialstructure represented by formula —CR⁷═CR⁷— (R⁷ is as defined above); or(iii) R⁶ and nitrogen atom may form a bond so that an adjacent nitrogenatom and a group —CR⁶R⁷— form a partial structure represented by —N═CR⁷—(R⁷ is as defined above); and p is an integer of 0, 1 or 2, providedthat when both E and G are groups —(CR⁶R⁷)_(p)— at the same time, p dosenot represent 0 and at least one of E and G represent group —CR⁶R⁷—);(3) —CO—; (4) —CS—; (5) —NR⁸— (wherein R⁸ represents: (i) hydrogen atom;(ii) formula —COR⁹ (wherein R⁹ represents a C₁₋₆ alkyl group, anoptionally substituted aryl C₁₋₄ alkyl group, an optionally substitutedaryl group, an optionally substituted heteroaryl C₁₋₄ alkyl group or anoptionally substituted heteroaryl group); (iii) —S(O)_(n)R¹⁰ (whereinR¹⁰ represents a C₁₋₆ alkyl group, an optionally substituted aryl C₁₋₄alkyl group, an optionally substituted aryl group, an optionallysubstituted heteroaryl C₁₋₄ alkyl group or an optionally substitutedheteroaryl group; and n is an integer of 0, 1 or 2); (iv) a C₁₋₁₀ alkylgroup optionally substituted with any of one or more groups defined inthe following A group; (v) a C₂₋₁₀ alkenyl group optionally substitutedwith any of one or more groups defined in the following A group; (vi) aC₂₋₁₀ alkynyl group optionally substituted with any of one or moregroups defined in the following A group; or (vii) a C₃₋₈ cycloalkylgroup optionally fused with an optionally substituted benzene ring andoptionally substituted with a C₁₋₄ alkyl group); (6) —SO—; or (7) —SO₂—;J represents: (1) nitrogen atom or (2) carbon atom or nitrogen atomwhich is substituted with any one or more selected from: (i) hydrogenatom; (ii) amino group; (iii) cyano group; (iv) a C₁₋₆ alkyl groupoptionally substituted with a halogen atom; (v) a C₁₋₆alkylaminosulfonyl group; (vi) an optionally substituted aryl group; and(vii) an optionally substituted saturated or unsaturated heterocyclicring, K and L are the same as or different from each other and eachrepresents carbon atom or nitrogen atom, a ring formed by K, E, G. J andL in the above formula (I) represents a saturated or unsaturated 5- or6-membered ring, M represents: (1) hydrogen atom; (2) halogen atom; (3)cyano group; (4) a C₁₋₆ alkyl group optionally substituted with any ofone or more groups defined in the following A group; (5) formula—NR¹¹R¹²— (wherein R¹¹ and R¹² are the same as or different from eachother and each represents: (i) hydrogen atom; (ii) any group defined inthe following A group; (iii) a C₁₋₆ alkyl group optionally substitutedwith any of one or more groups defined in the following A group; (iv) aC₁₋₄ alkylacyl group; (v) an optionally substituted aryl C₁₋₄ alkylgroup; (vi) an optionally substituted heteroaryl C₁₋₄ alkyl group; (vii)an optionally substituted aryl group; or (viii) an optionallysubstituted heteroaryl group); (6) —OR¹³ (wherein R¹³ representshydrogen atom, a C₁₋₆ alkyl group optionally substituted with any of oneor more groups defined in the following A group, a C₁₋₄ alkylacyl group,an optionally substituted aryl C₁₋₄ alkyl group, an optionallysubstituted heteroaryl C₁₋₄ alkyl group, an optionally substituted arylgroup or an optionally substituted heteroaryl group); (7) —S(O)_(q)R¹⁴(wherein R¹⁴ represents a C₁₋₆ alkyl group, an optionally substitutedaryl C₁₋₄ alkyl group, an optionally substituted aryl group, anoptionally substituted heteroaryl C₁₋₄ alkyl group or an optionallysubstituted heteroaryl group; and q is an integer of 0, 1 or 2); (8) anoptionally substituted C₂₋₁₀ alkenyl group; (9) an optionallysubstituted C₂₋₁₀ alkynyl group; (10) a C₁₋₆ alkoxy group optionallysubstituted with any of one or more groups defined in the following Agroup; (11) a C₁₋₆ alkylthio group optionally substituted with any ofone or more groups defined in the following A group; (12) an optionallysubstituted aryl group; or (13) an optionally substituted heteroarylgroup, the partial structure

represents a single or double bond, and the A group defined aboverepresents the group consisting of: (1) halogen atom, (2) hydroxy group,(3) nitro group, (4) cyano group, (5) carboxy group, (6) a C₁₋₆alkyloxycarbonyl group, (7) a group represented by the formula—S(O)_(r)R¹⁵ (wherein r is an integer of 0, 1 or 2; and R¹⁵ represents:(i) hydrogen atom; (ii) a C₁₋₆ alkyl group; (iii) a group represented bythe formula —NR¹⁶R¹⁷ (wherein R¹⁶ and R¹⁷ are the same as or differentfrom each other and each represents hydrogen atom, a C₁₋₆ alkyl groupoptionally substituted with an optionally substituted aryl group, a C₁₋₄alkylacyl group, an optionally substituted aryl C₁₋₄ alkyl group, anoptionally substituted heteroaryl C₁₋₄ alkyl group, an optionallysubstituted aryl group or an optionally substituted heteroaryl group);(iv) an optionally substituted aryl C₁₋₄ alkyl group; (v) an optionallysubstituted aryl group; (vi) an optionally substituted heteroaryl C₁₋₄alkyl group; or (vii) an optionally substituted heteroaryl group); (8) agroup represented by the formula —NR¹⁸R¹⁹ (wherein R¹⁸ and R¹⁹ are thesame as or different from each other and each represents hydrogen atom,a C₁₋₆ alkyl group or a C₁₋₄ alkylacyl group); (9) a C₁₋₆ alkyl group;(10) a C₁₋₆ alkoxy group; (11) a C₃₋₈ cycloalkyl group optionallysubstituted with a C₁₋₄ alkyl group; (12) a C₁₋₄ alkoxy C₁₋₆ alkylgroup; (13) a saturated 3- to 8-membered heterocyclic ring optionallysubstituted with a C₁₋₄ alkyl group; (14) an optionally substituted arylgroup; and (15) an optionally substituted heteroaryl group, providedthat in the above definition, (1) the case where both K and L arenitrogen atoms; and (2) the case where K is nitrogen atom, L is carbonatom, A and B are groups represented by the formula —(CR¹R²)_(m)—(wherein both R¹ and R² represent hydrogen atoms; and m is 1), and J iscarbon atom substituted with any group selected from: (i) amino group;(ii) cyano group; (iii) aminosulfonyl group in which the nitrogen atomis substituted with a straight or branched C₁₋₆ alkyl group; and (iv)1H-tetrazol-5-yl group, are excluded), a pharmacologically acceptablesalt thereof or hydrates thereof.
 2. The compound as claimed in claim 1,a pharmacologically acceptable salt thereof or hydrates thereof, whereinat least one selected from A, B and D are nitrogen atom, oxygen atom,sulfur atom or a group represented by the formula —NR³—, —CO— or—(CR¹R²)_(m)— (wherein R¹, R², R³ and m have the same meanings asdefined above).
 3. The compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof, whereinat least one of A and B is a group represented by the formula—(CR¹R²)_(m)— (wherein R¹, R² and m have the same meanings as definedabove).
 4. The compound as claimed in claim 1, a pharmacologicallyacceptable salt thereof or hydrates thereof, wherein D is nitrogen,oxygen, sulfur or a group represented by the formula —NR³— (wherein R³has the same meaning as defined above).
 5. The compound as claimed inclaim 1, a pharmacologically acceptable salt thereof or hydratesthereof, wherein D is a group represented by the formula —NR³— (whereinR³ has the same meaning as defined above).
 6. The compound as claimed inclaim 1, a pharmacologically acceptable salt thereof or hydratesthereof, wherein the partial structure -A

B

D- is a group represented by the formula: —CH₂—CHR²—CHR²—;—CH₂—CHR²—NR³—; —CH═CR²—CHR²——CH₂—CHR²—O—; —CH₂—CHR²—S—;—CR²═N—NR³——CH═CR²—NR³—; —CR²═CR²—NR³—, —NH—CR²═CR²——N═CR²—CHR²—;—(CH₂)₂—CR²—NR³—; —(CH₂)₃—CR²—NR³——CH₂—CO—NR³—; —CO—NR³—CO—;—CO—NR³—NR³——NR³—CO—NR³—; —CH₂—CS—NR³—; —CS—NR³—CS——CS—NR³—NR³— or—NR³—CS—NR³— (wherein R² and R³ have the same meanings as defined aboveand each R² and R³ are the same or different groups).
 7. The compound asclaimed in claim 6, a pharmacologically acceptable salt thereof orhydrates thereof, wherein at least one selected from R² and R³ are thesame as or different from each other and each represents hydrogen atom,a C₁₋₆ alkyl group, a C₂₋₆ alkynyl group, a C₁₋₆ alkoxy C₁₋₆ alkyl groupor a C₁₋₆ alkyl-aryl group.
 8. The compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof, wherein Kis nitrogen atom and L is carbon atom.
 9. The compound as claimed inclaim 1, a pharmacologically acceptable salt thereof or hydratesthereof, wherein K and L are carbon atoms.
 10. The compound as claimedin claim 1, a pharmacologically acceptable salt thereof or hydratesthereof, wherein E or G is nitrogen atom.
 11. The compound as claimed inclaim 1, a pharmacologically acceptable salt thereof or hydratesthereof, wherein E or G is a group represented by the formula—(CR⁶R⁷)_(p)— (wherein R⁶ and R⁷ have the same meanings as definedabove).
 12. The compound as claimed in claim 1, a pharmacologicallyacceptable salt thereof or hydrates thereof, wherein the partialstructure

E

G

is a group represented by the formula —[CH(R⁷)]₂—, —N═CR⁷—, —CR⁷═N—,—[CH(R⁷)]₃—, —CR⁷═CR⁷—CR⁷═, —N═CR⁷—CR⁷═ or —CR⁷═CR⁷—N═ (wherein R⁷ hasthe same meaning as defined above).
 13. The compound as claimed in claim12, a pharmacologically acceptable salt thereof or hydrates thereof,wherein R⁷s are the same as or different from each other and eachrepresents hydrogen atom or a C₁₋₆ alkyl group.
 14. The compound asclaimed in claim 1, a pharmacologically acceptable salt thereof orhydrates thereof, wherein J is a carbon atom or nitrogen atomsubstituted with any one group selected from (1) an aryl group; and (2)a saturated or unsaturated heterocyclic ring, each being optionallysubstituted.
 15. The compound as claimed in claim 1, a pharmacologicallyacceptable salt thereof or hydrates thereof, wherein J is a carbon atomor nitrogen atom substituted with anyone group selected from phenylgroup; pyridyl group; thienyl group; and furyl group, each beingoptionally substituted.
 16. The compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof, wherein Jis a carbon atom or nitrogen atom substituted with a phenyl groupoptionally substituted with 1 to 3 groups selected from a halogen atom;and an optionally halogenated C₁₋₆ alkyl group and C₁₋₆ alkoxy group.17. The compound as claimed in claim 1, a pharmacologically acceptablesalt thereof or hydrates thereof, wherein M is (1) hydrogen, (2) ahalogen atom, (3) cyano group, (4) a C₁₋₆ alkyl group optionallysubstituted with any one or more groups defined in the above A group,(5) a C₁₋₆ alkoxy group optionally substituted with any one or moregroups defined in the above A group, or (6) an amino group optionallysubstituted with any one or more groups defined in the above A group.18. The compound as claimed in claim 1, a pharmacologically acceptablesalt thereof or hydrates thereof, wherein M is hydrogen atom, a C₁₋₆alkyl group, a C₁₋₆ alkoxyl group or a C₁₋₆ alkylthio group.
 19. Thecompound as claimed in claim 1, a pharmacologically acceptable saltthereof or hydrates thereof, wherein M is methyl group.
 20. The compoundas claimed in claim 1, a pharmacologically acceptable salt thereof orhydrates thereof, wherein A and B are groups represented by the formula—(CR¹′R²′)_(m′)— (wherein R¹′ and R²′ are the same as or different fromeach other and each represents hydrogen or a C₁₋₆ alkyl group; and m′ isan integer from 1 to 3), D is a group represented by the formula —NR³—(wherein R³ has the same meaning as defined above), E is nitrogen and Gis a group represented by the formula ═CR⁸— (wherein R⁸ has the samemeaning as defined above).
 21. The compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof, whereinthe partial structure -A

B

is a group represented by the formula —CR²═CR²— (wherein R² representshydrogen atom or a C₁₋₆ alkyl group); D is a group represented by theformula —NR³— (wherein R³ has the same meaning as defined above); E isnitrogen atom; and G is a group represented by the formula ═CR⁸—(wherein R⁸ has the same meaning as defined above).
 22. The compound asclaimed in claim 1, a pharmacologically acceptable salt thereof orhydrates thereof, wherein A is a group represented by the formula—(CR¹R²)_(m′)— (wherein R¹ and R² are the same as or different from eachother and each represents hydrogen atom or a C₁₋₆ alkyl group; and m′ isan integer from 1 to 3); B is a group represented by the formula —CO— or—CS—; D is a group represented by the formula —NR³— (wherein R³ has thesame meanings as defined above); E is nitrogen atom; and G is a grouprepresented by the formula ═CR⁸— (wherein R⁸ has the same meaning asdefined above).
 23. A compound represented by the formula:

(wherein R², R³ and the partial structure

have the same meanings as defined above; M′ represents hydrogen atom, ahalogen atom or a C₁₋₆ alkyl group; R⁷′ represents hydrogen atom or aC₁₋₆ alkyl group; and W′ represents an optionally substituted aryl groupor an optionally substituted saturated or unsaturated heterocyclicring), a pharmacologically acceptable salt thereof or hydrates thereof.24. A compound represented by the formula:

(wherein R², R³, R⁷′, M′, W′ and the partial structure

have the same meanings as defined above), a pharmacologically acceptablesalt thereof or hydrates thereof.
 25. A compound represented by theformula:

(wherein R², R³, R⁷′, M′, W′ and the partial structure

have the same meanings as defined above), a pharmacologically acceptablesalt thereof or hydrates thereof.
 26. A compound represented by theformula:

(wherein R², R³, R⁷′, M′, W′ and the partial structure

have the same meanings as defined above), a pharmacologically acceptablesalt thereof or hydrates thereof.
 27. A compound represented by theformula:

(wherein R², R³, R⁷′, M′, W′ and the partial structure

have the same meanings as defined above), a pharmacologically acceptablesalt thereof or hydrates thereof.
 28. A compound represented by theformula:

(wherein R², R³, R⁷′, M′, W′ and a partial structure

have the same meanings as defined above), a pharmacologically acceptablesalt thereof or hydrates thereof.
 29. The compound as claimed in claim1, a pharmacologically acceptable salt thereof or hydrates thereof,wherein the compound is any one selected from the group consisting of:8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;8-(1-ethylpropyl)-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;3-mesityl-8-[2-methoxy-1-(methoxymethyl)ethyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;8-benzyl-3-mesityl-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;3-mesityl-8-[1-(methoxymethyl)propyl]-2,5-dimethyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;3-mesityl-2,5-dimethyl-8-(1-propylbutyl)-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;2-ethyl-8-(1-ethylpropyl)-3-mesityl-5-methyl-7,8-dihydro-6H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;8-(1-ethylpropyl)-2,5-dimethyl-3-(2,4,6-trimethyl-3-pyridyl)-8H-pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine;6-mesityl-2,4,7-trimethyl-2H-dipyrazolo[1,5-a:4,3-e]pyrimidine;9-(cyclopropylmethyl)-8-ethyl-3-mesityl-2,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine;2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c]quinolin-1-yl)butyl methyl ether;1-(1-ethylpropyl)-6-mesityl-4-methy-1H-pyrrolo[3,2-c][1,7]naphthyridine;and 2-(6-mesityl-4-methyl-1H-pyrrolo[3,2-c][1,5]naphthyridin-1-yl)butylmethyl ether.
 30. A medicament which comprises the compound as claimedin claim 1, a pharmacologically acceptable salt thereof or hydratesthereof.
 31. The medicament as claimed in claim 30, which is an agentfor treating or preventing diseases to which at least one ofcorticotrophin-releasing factor (hereinafter, referred to as “CRF”) anda CRF receptor relate.
 32. The medicament as claimed in claim 30, whichis a CRF receptor antagonist.
 33. The medicament as claimed in claim 30,which is an agent for treating or preventing depression, depressivesymptom or mania.
 34. The medicament as claimed in claim 33 in which thedepressive symptom is great depression, monostotic depression, recurrentdepression, infant tyrannism by depression or postpartum depression. 35.The medicament as claimed in claim 30, which is an agent for treating orpreventing anxiety, generalized anxiety disorder, panic disorder,phobia, compulsive disorder, posttraumatic stress disorder, Tourettesyndrome, autism, emotional disorder, sentimental disorder, bipolardisorder, cyclothymia or schizophrenia.
 36. The medicament as claimed inclaim 30, which is an agent for treating or preventing peptic ulcer,irritable bowel syndrome, ulcerative colitis, Crohn's disease, diarrhea,coprostasis, postoperational ileus, gastrointestinal functionabnormality associated with stress or neural vomiting.
 37. Themedicament as claimed in claim 30, which is an agent for treating orpreventing Alzheimer disease, Alzheimer-type senile dementia,neurodegenerative disease, multi-infarct dementia, senile dementia,neurotic anorexia, diet disorder, obesity, diabetes, alcohol dependence,pharmacophilia, drug abstinence symptoms, alcohol abstinence symptoms,sleep disorder, insomnia, migraine, stress headache, myotonic headache,ischemic neuropathy, excitation toxic neuropathy, cerebral apoplexy,progressive supranuclear palsy, amyotrophic lateral sclerosis, multiplesclerosis, muscular convulsion, chronic fatigue syndrome, mental socialgrowth failure, epilepsy, head trauma, spinal trauma, graphospasm,spasmodic torticollis, muscular convulsion, neck-shoulder-arm syndrome,primary glaucoma, Meniere syndrome, autonomic imbalance, alopecia,neurosis, hypertension, cardiovascular disorder, tachycardia, congestivecardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome,infant sudden death syndrome, inflammatory disorder, pain, allergicdisease, impotence, climacteric disorder, fertilization disorder,infertility, cancer, immune function abnormality upon infection withHIV, immune function abnormality by stress, hemorrhagic stress, Cushingsyndrome, thyroid function disorder, encephalomyelitis, acromegaly,incontinence or osteoporosis.
 38. A method for treating or preventing adisease to which at least one of CRF and CRF receptor relate, byadministering a pharmaceutical effective dose of the compound as claimedin claim 1, a pharmacologically acceptable salt thereof or hydratesthereof to a patient.
 39. A method for treating or preventing a diseaseagainst which CRF receptor antagonism is efficacious, by administering apharmaceutical effective dose of the compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof to apatient.
 40. A method for treating or preventing depression, depressivesymptom such as great depression, monostotic depression, recurrentdepression, infant tyrannism by depression, postpartum depression etc.,mania, anxiety, generalized anxiety disorder, panic disorder, phobia,compulsive disorder, posttraumatic stress disorder, Tourette syndrome,autism, emotional disorder, sentimental disorder, bipolar disorder,cyclothymia, schizophrenia, peptic ulcer, irritable bowel syndrome,ulcerative colitis, Crohn's disease, diarrhea, coprostasis,postoperational ileus, gastrointestinal function abnormality associatedwith stress or neural vomiting, Alzheimer disease, Alzheimer-type seniledementia, neurodegenerative disease, multi-infarct dementia, seniledementia, neurotic anorexia, diet disorder, obesity, diabetes, alcoholdependence, pharmacophilia, drug abstinence symptoms, alcohol abstinencesymptoms, sleep disorder, insomnia, migraine, stress headache, myotonicheadache, ischemic neuropathy, excitation toxic neuropathy, cerebralapoplexy, progressive supranuclear palsy, amyotrophic lateral sclerosis,multiple sclerosis, muscular convulsion, chronic fatigue syndrome,mental social growth failure, epilepsy, head trauma, spinal trauma,graphospasm, spasmodic torticollis, muscular convulsion,neck-shoulder-arm syndrome, primary glaucoma, Meniere syndrome,autonomic imbalance, alopecia, neurosis, hypertension, cardiovasculardisorder, tachycardia, congestive cardioplegia, hyperpnea syndrome,bronchial asthma, apnea syndrome, infant sudden death, syndrome,inflammatory disorder, pain, allergic disease, impotence, climactericdisorder, fertilization disorder, infertility, cancer, immune functionabnormality upon infection with HIV, immune function abnormality bystress, hemorrhagic stress, Cushing syndrome, thyroid function disorder,encephalomyelitis, acromegaly, incontinence or osteoporosis, byadministering a pharmaceutical effective dose of the compound as claimedin claim 1, a pharmacologically acceptable salt thereof or hydratesthereof to a patient.
 41. Use of the compound as claimed in claim 1, apharmacologically acceptable salt thereof or hydrates thereof forproducing an agent for treating or preventing diseases to which at leastone of CRF and CRF receptor relate.
 42. Use of the compound as claimedin claim 1, a pharmacologically acceptable salt thereof or hydratesthereof for producing an agent for treating or preventing diseasesagainst which CRF receptor antagonism is efficacious.
 43. Use of thecompound as claimed in claim 1, a pharmacologically acceptable saltthereof or hydrates thereof for producing an agent for treating orpreventing depressive symptom such as great depression, monostoticdepression, recurrent depression, infant tyrannism by depression andpostpartum depression, depression, mania, anxiety, generalized anxietydisorder, panic disorder, phobia, compulsive disorder, posttraumaticstress disorder, Tourette syndrome, autism, emotional disorder,sentimental disorder, bipolar disorder, cyclothymia, schizophrenia,peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'sdisease, diarrhea, coprostasis, postoperational ileus, gastrointestinalfunction abnormality associated with stress, neural vomiting, Alzheimerdisease, Alzheimer-type senile dementia, neurodegenerative disease,multi-infarct dementia, senile dementia, neurotic anorexia, dietdisorder, obesity, diabetes, alcohol dependence, pharmacophilia, drugabstinence symptoms, alcohol abstinence symptoms, sleep disorder,insomnia, migraine, stress headache, myotonic headache, ischemicneuropathy, excitation toxic neuropathy, cerebral apoplexy, progressivesupranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis,muscular convulsion, chronic fatigue syndrome, mental social growthfailure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodictorticollis, muscular convulsion, neck-shoulder-arm syndrome, primaryglaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis,hypertension, cardiovascular disorder, tachycardia, congestivecardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome,infant sudden death, syndrome, inflammatory disorder, pain, allergicdisease, impotence, climacteric disorder, fertilization disorder,infertility, cancer, immune function abnormality upon infection withHIV, immune function abnormality by stress, hemorrhagic stress, Cushingsyndrome, thyroid function disorder, encephalomyelitis, acromegaly,incontinence or osteoporosis.